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#redirect[[5-HT1A receptor]]
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{{DISPLAYTITLE:5-HT<sub>1A</sub> receptor}}
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{{PBB|geneid=3350}}
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The '''5-HT<sub>1A</sub> receptor''' is a subtype of [[5-HT receptor]] that binds the [[endogenous]] [[neurotransmitter]] [[serotonin]] (5-hydroxytryptamine, 5-HT). It is a [[G protein-coupled receptor]] (GPCR) that is coupled to [[Gi alpha subunit|G<sub>i</sub>/G<sub>o</sub>]] and mediates [[IPSP|inhibitory]] [[neurotransmission]]. ''HTR1A'' denotes the [[human]] [[gene]] encoding for the [[Receptor (biochemistry)|receptor]].<ref name="pmid2591972">{{cite journal | author = Gilliam TC, Freimer NB, Kaufmann CA, Powchik PP, Bassett AS, Bengtsson U, Wasmuth JJ | title = Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia | journal = Genomics | volume = 5 | issue = 4 | pages = 940–4 | year = 1989 | month = November | pmid = 2591972 | url = | doi = 10.1016/0888-7543(89)90138-9 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HTR1A 5-hydroxytryptamine (serotonin) receptor 1A | url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3350 | accessdate = }}</ref>
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== Distribution ==
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The 5-HT<sub>1A</sub> receptor is the most widespread of all the 5-HT receptors. In the [[central nervous system]], 5-HT<sub>1A</sub> receptors exist in the [[cerebral cortex]], [[hippocampus]], [[Septum pellucidum|septum]], [[amygdala]], and [[Raphe nuclei|raphe nucelus]] in high densities, while low amounts also exist in the [[basal ganglia]] and [[thalamus]].<ref name="pmid9935065">{{cite journal | author = Ito H, Halldin C, Farde L. | title = Localization of 5-HT1A receptors in the living human brain using [carbonyl-11C]WAY-100635: PET with anatomic standardization technique. | journal = J Nucl Med. | volume = 40 | issue = 1 | pages = 102–109 | year = 1999 | pmid = 9935065 }}</ref><ref name="urlSerotonin Receptor Subtypes and Ligands">{{cite web | url = http://www.acnp.org/g4/GN401000039/Ch039.html | title = Serotonin Receptor Subtypes and Ligands | accessdate = 2008-04-11 | author = Glennon RA, Dukat M, Westkaemper RB | authorlink = | coauthors = | date = 2000-01-01 | work = | publisher = American College of Neurophyscopharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}</ref><ref name="pmid18761712">{{cite journal | author = de Almeida J, Mengod G. | title = Serotonin 1A receptors in human and monkey prefrontal cortex are mainly expressed in pyramidal neurons and in a GABAergic interneuron subpopulation: implications for schizophrenia and its treatment. | journal = J Neurochem. | volume = 107 | issue = 2 | pages = 488–496 | year = 2008 | pmid = 18761712 | doi = 10.1111/j.1471-4159.2008.05649.x }}</ref> The 5-HT<sub>1A</sub> receptors in the raphe nucleus are largely [[somatodendritic]] [[autoreceptor]]s.<ref name="urlSerotonin Receptor Subtypes and Ligands"/>
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== Function ==
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=== Neuromodulation ===
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5-HT<sub>1A</sub> [[Receptor (biochemistry)|receptor]] [[agonist]]s decrease [[blood pressure]] and [[heart rate]] or cause [[hypotension]] via a central mechanism, by inducing [[peripheral]] [[vasodilation]], and by stimulating the [[vagus nerve]].<ref name="pmid1819150">{{cite journal | author = Dabiré H. | title = Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation. | journal = Therapie. | volume = 46 | issue = 6 | pages = 421–9 | year = 1991 | pmid = 1819150 }}</ref> These effects are the result of activation of 5-HT<sub>1A</sub> receptors within the [[rostral ventrolateral medulla]].<ref name="pmid1819150"/> The [[sympatholytic]] [[antihypertensive]] [[drug]] [[urapidil]] is an [[α1-adrenergic receptor|α<sub>1</sub>-adrenergic receptor]] [[receptor antagonist|antagonist]] and [[α2-adrenergic receptor|α<sub>2</sub>-adrenergic receptor]] agonist, as well as 5-HT<sub>1A</sub> receptor agonist, and it has been demonstrated that the latter property contributes to its overall therapeutic effects.<ref name="pmid1855130">{{cite journal |author=Ramage AG |title=The mechanism of the sympathoinhibitory action of urapidil: role of 5-HT1A receptors |journal=Br. J. Pharmacol. |volume=102 |issue=4 |pages=998–1002 |year=1991 |month=April |pmid=1855130 |pmc=1917978 |doi= |url=}}</ref><ref name="pmid2569265">{{cite journal | author = Kolassa N, Beller KD, Sanders KH. | title = Involvement of brain 5-HT1A receptors in the hypotensive response to urapidil. | journal = Am J Cardiol. | volume = 64 | issue = 7 | pages = 7D–10D | year = 1989 | pmid = 2569265 | doi = 10.1016/0002-9149(89)90688-7 }}</ref>
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Vasodilation of the [[blood vessel]]s in the [[skin]] via central 5-HT<sub>1A</sub> activation increases [[heat]] [[heat transfer|dissipation]] from the organism out into the environment, causing a decrease in [[body temperature]] or [[hypothermia]].<ref name="pmid16455061">{{cite journal | author = Ootsuka Y, Blessing WW. | title = Activation of 5-HT1A receptors in rostral medullary raphé inhibits cutaneous vasoconstriction elicited by cold exposure in rabbits. | journal = Brain Res. | volume = 1073-1074 | pages = 252–61 | year = 2006 | pmid = 16455061 | doi = 10.1016/j.brainres.2005.12.031 }}</ref><ref name="pmid17702902">{{cite journal | author = Rusyniak DE, Zaretskaia MV, Zaretsky DV, DiMicco JA. | title = 3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors. | journal = J Pharmacol Exp Ther. | volume = 323 | issue = 2 | pages = 477–487 | year = 2007 | pmid = 17702902 | doi = 10.1124/jpet.107.126169 }}</ref>
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Activation of central 5-HT<sub>1A</sub> receptors triggers the release or inhibition of [[norepinephrine]] depending on species, presumably from the [[locus coeruleus]], which then reduces or increases neuronal tone to the [[iris sphincter muscle]] by modulation of [[postsynaptic]] [[α2-adrenergic receptor|α<sub>2</sub>-adrenergic receptor]]s within the [[Edinger-Westphal nucleus]], resulting in [[pupil dilation]] or [[mydriasis]] in [[rodent]]s, and [[pupil]] [[constriction]] or [[miosis]] in [[primate]]s like [[human]]s.<ref name="pmid15087245">{{cite journal | author = Yu Y, Ramage AG, Koss MC. | title = Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats. | journal = Eur J Pharmacol. | volume = 489 | issue = 3 | pages = 207–213 | year = 2004 | pmid = 15087245 | doi = 10.1016/j.ejphar.2004.03.007 }}</ref><ref name="pmid8982715">{{cite journal | author = Prow MR, Martin KF, Heal DJ | title = 8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation | journal = Eur J Pharmacol. | volume = 317 | issue = 1 | pages = 21–8 | year = 1996 | pmid = 8982715 | doi = 10.1016/S0014-2999(96)00693-0 }}</ref><ref name="pmid7697953">{{cite journal | author = Fanciullacci M, Sicuteri R, Alessandri M, Geppetti P | title = Buspirone, but not sumatriptan, induces miosis in humans: relevance for a serotoninergic pupil control | journal = Clinical Pharmacology and Therapeutics | volume = 57 | issue = 3 | pages = 349–55 | year = 1995 | month = March | pmid = 7697953 | doi = 10.1016/0009-9236(95)90161-2 | url = }}</ref>
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5-HT<sub>1A</sub> receptor agonists like [[buspirone]]<ref>{{cite journal |last=Cohn |first=JB |coauthors=Rickels K |year=1989 |title=A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety |journal=Curr Med Res Opin. |volume=11 |issue=5 |pages=304–320 |pmid=2649317 |doi=10.1185/03007998909115213 |doi_brokendate=2010-01-04 }}</ref> and [[flesinoxan]]<ref name="pmid9169298">{{cite journal | author = Cryan JF, Redmond AM, Kelly JP, Leonard BE. | title = The effects of the 5-HT1A agonist flesinoxan, in three paradigms for assessing antidepressant potential in the rat. | journal = Eur Neuropsychopharmacol. | volume = 7 | issue = 2 | pages = 109–114 | year = 1997 | pmid = 9169298 | doi = 10.1016/S0924-977X(96)00391-4 }}</ref> show efficacy in relieving [[anxiety]]<ref name="pmid9724773">{{cite journal | author = Parks CL, Robinson PS, Sibille E, Shenk T, Toth M | title = Increased anxiety of mice lacking the serotonin1A receptor | journal = Proc Natl Acad Sci U S A. | volume = 195 | issue = 18 | pages = 10734–9 | year = 1998 | pmid = 9724773 | doi = 10.1073/pnas.95.18.10734 | pmc = 27964 }}</ref> and [[Depression (mood)|depression]],<ref name="pmid2883013">{{cite journal | author = Kennett GA, Dourish CT, Curzon G | title = Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression | journal = Eur J Pharmacol. | volume = 134 | issue = 3 | pages = 265–74 | year = 1987 | pmid = 2883013 | doi = 10.1016/0014-2999(87)90357-8 }}</ref> and [[buspirone]] and [[tandospirone]] are currently approved for these indications in various parts of the world. Others such as [[gepirone]],<ref name="pmid15643103">{{cite journal | author = Keller MB, Ruwe FJ, Janssens CJ, Sitsen JM, Jokinen R, Janczewski J | title = Relapse prevention with gepirone ER in outpatients with major depression | journal = Journal of Clinical Psychopharmacology | volume = 25 | issue = 1 | pages = 79–84 | year = 2005 | month = February | pmid = 15643103 | doi = 10.1097/01.jcp.0000150221.53877.d9| url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0271-0749&volume=25&issue=1&spage=79}}</ref> [[flesinoxan]],<ref name="pmid9169298">{{cite journal | author = Cryan JF, Redmond AM, Kelly JP, Leonard BE | title = The effects of the 5-HT1A agonist flesinoxan, in three paradigms for assessing antidepressant potential in the rat | journal = European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology | volume = 7 | issue = 2 | pages = 109–14 | year = 1997 | month = May | pmid = 9169298 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/S0924-977X(96)00391-4}}</ref> [[flibanserin]],<ref>{{cite journal|author = Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R | url=http://www.nature.com/bjp/journal/v139/n7/full/0705341a.html | title= Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. | journal= Br J Pharmacol.| volume=139| issue=7| pages= 1281–8| year= 2003 | month= August | doi= 10.1038/sj.bjp.0705341|pmid = 12890707|pmc = 1573953}}</ref> and [[PRX-00023]]<ref name="pmid17263189">{{cite journal | author = de Paulis T. | title = Drug evaluation: PRX-00023, a selective 5-HT1A receptor agonist for depression. | journal = Curr Opin Investig Drugs. | volume = 8 | issue = 1 | pages = 78–86 | year = 2007 | pmid = 17263189 }}</ref> have also been investigated, though none have been fully developed and approved as of yet. Some of the [[atypical antipsychotic]]s like [[aripiprazole]]<ref name="pmid17242925">{{cite journal
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|author = Stark, AD et al. | title = Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies. | journal = Psychopharmacology (Berl) | volume = 190 | issue = 3 | pages = 373–382 | doi = 10.1007/s00213-006-0621-y | pmid = 17242925 | year = 2007}}</ref> are also [[partial agonist]]s at the 5-HT<sub>1A</sub> receptor and are often used in low doses as augmentations to standard [[antidepressant]]s like the [[selective serotonin reuptake inhibitor]]s (SSRIs).<ref>{{cite journal|last=Vega|first=JAW|coauthors=Mortimer AM, Tyson PJ|year=2003|month=May|title=Conventional Antipsychotic Prescription in Unipolar Depression, I: An Audit and Recommendations for Practice |journal=The Journal of Clinical Psychiatry|volume=64|issue=5|pages=568–574|publisher=Physicians Postgraduate Press|issn=1555-2101|url=http://www.psychiatrist.com/abstracts/abstracts.asp?abstract=200305/050311.htm|accessdate=2009-05-28|pmid=12755661}}</ref>
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5-HT<sub>1A</sub> autoreceptor desensitization and increased 5-HT<sub>1A</sub> receptor postsynaptic activation via general increases in serotonin levels by serotonin [[Precursor (chemistry)|precursor]] [[Dietary supplement|supplementation]], [[serotonin reuptake inhibitor|serotonin reuptake inhibition]], or [[monoamine oxidase]] [[enzyme inhibition|inhibition]] has been shown to be a major mediator in the therapeutic benefits of most mainstream [[antidepressant]] [[Dietary supplement|supplement]]s and [[pharmaceutical]]s, including serotonin precursors like [[L-tryptophan]] and [[5-hydroxytryptophan|5-HTP]], [[selective serotonin reuptake inhibitor]]s (SSRIs), [[serotonin-norepinephrine reuptake inhibitor]]s (SNRIs), [[tricyclic antidepressant]]s (TCAs), [[tetracyclic antidepressant]]s (TeCAs), and [[monoamine oxidase inhibitor]]s (MAOIs).<ref name="pmid11212592">{{cite journal | author = Blier P, Abbott FV | title = Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain | journal = Journal of Psychiatry & Neuroscience : JPN | volume = 26 | issue = 1 | pages = 37–43 | year = 2001 | month = January | pmid = 11212592 | pmc = 1408043 | doi = | url = http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-26/issue-1/pdf/pg37.pdf}}</ref> 5-HT<sub>1A</sub> receptor activation likely plays a significant role in the positive effects of serotonin [[releasing agent]]s (SRAs) like [[MDMA]] ("[[Ecstasy (drug)|Ecstasy]]") as well.<ref name="pmid15908091">{{cite journal | author = Morley KC, Arnold JC, McGregor IS | title = Serotonin (1A) receptor involvement in acute 3,4-methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat | journal = Progress in Neuro-psychopharmacology & Biological Psychiatry | volume = 29 | issue = 5 | pages = 648–57 | year = 2005 | month = June | pmid = 15908091 | doi = 10.1016/j.pnpbp.2005.04.009 | url = }}</ref><ref name="pmid17383105">{{cite journal | author = Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS | title = A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy") | journal = Neuroscience | volume = 146 | issue = 2 | pages = 509–14 | year = 2007 | month = May | pmid = 17383105 | doi = 10.1016/j.neuroscience.2007.02.032 | url = }}</ref>
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5-HT<sub>1A</sub> receptors in the [[dorsal raphe nucleus]] are co-localized with [[Tachykinin receptor 1|neurokinin 1]] (NK<sub>1</sub>) receptors and have been shown to inhibit the release of [[substance P]], their [[endogenous]] [[ligand]].<ref name="pmid16950604">{{cite journal | author = Gobbi G, Cassano T, Radja F, Morgese MG, Cuomo V, Santarelli L, Hen R, Blier P| title = Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function | journal = European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology | volume = 17 | issue = 5 | pages = 328–38 | year = 2007 | month = April | pmid = 16950604 | doi = 10.1016/j.euroneuro.2006.07.004 | url = }}</ref><ref>Baker KG, Halliday GM, Hornung J-P, Geffen LB, Cotton RGH, Tork I. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1720227&query_hl=16&itool=pubmed_docsum Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus.] Neuroscience. 1991;42(3):757-75.</ref> In addition to being [[antidepressant]] and [[anxiolytic]] in effect, 5-HT<sub>1A</sub> receptor activation has also been demonstrated to be [[antiemetic]]<ref name="pmid8013549">{{cite journal | author = Lucot JB | title = Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin | journal = European Journal of Pharmacology | volume = 253 | issue = 1-2 | pages = 53–60 | year = 1994 | month = February | pmid = 8013549 | doi = 10.1016/0014-2999(94)90756-0| url = }}</ref><ref name="pmid12401641">{{cite journal | author = Oshima T, Kasuya Y, Okumura Y, Terazawa E, Dohi S | title = Prevention of nausea and vomiting with tandospirone in adults after tympanoplasty | journal = Anesthesia and Analgesia | volume = 95 | issue = 5 | pages = 1442–5, table of contents | year = 2002 | month = November | pmid = 12401641 | doi = 10.1097/00000539-200211000-00063| url = http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=12401641}}</ref> and [[analgesic]],<ref name="pmid12595749">{{cite journal | author = Bardin L, Tarayre JP, Malfetes N, Koek W, Colpaert FC | title = Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain | journal = Pharmacology | volume = 67 | issue = 4 | pages = 182–94 | year = 2003 | month = April | pmid = 12595749 | doi = 10.1159/000068404 | url = }}</ref><ref name="pmid16425670">{{cite journal | author = Colpaert FC | title = 5-HT(1A) receptor activation: new molecular and neuroadaptive mechanisms of pain relief | journal = Current Opinion in Investigational Drugs (London, England : 2000) | volume = 7 | issue = 1 | pages = 40–7 | year = 2006 | month = January | pmid = 16425670 | doi = | url = }}</ref> and all of these properties may be mediated in part or full, depending on the property in question, by NK<sub>1</sub> receptor inhibition. Consequently, novel [[NK1 receptor antagonist|NK<sub>1</sub> receptor antagonists]] are now in use for the treatment of [[nausea]] and [[emesis]], and are also being investigated for the treatment of [[anxiety]] and [[Depression (mood)|depression]].<ref name="pmid15173897">{{cite journal | author = Blier P, Gobbi G, Haddjeri N, Santarelli L, Mathew G, Hen R. | title = Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response. | journal = J Psychiatry Neurosci. | volume = 29 | issue = 3 | pages = 208–218 | year = 2004 | pmid = 15173897 | pmc = 400690 }}</ref>
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5-HT<sub>1A</sub> receptor activation has been shown to increase [[dopamine]] release in the [[medial prefrontal cortex]], [[striatum]], and [[hippocampus]], and may be useful for improving the symptoms of [[schizophrenia]] and [[Parkinson's disease]].<ref name="pmid15189766">{{cite journal | author = Li Z, Ichikawa J, Dai J, Meltzer HY. | title = Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain. | journal = Eur J Pharmacol. | volume = 498 | issue = 1-3 | pages = 75–83 | year = 2004 | pmid = 15189766 | doi = 10.1016/j.ejphar.2004.04.028 }}</ref><ref name="pmid15906386">{{cite journal | author = Bantick RA, De Vries MH, Grasby PM. | title = The effect of a 5-HT1A receptor agonist on striatal dopamine release. | journal = Synapse. | volume = 57 | issue = 2 | pages = 67–75 | year = 2005 | pmid = 15906386 | doi = 10.1002/syn.20156 }}</ref> As mentioned above, some of the atypical antipsychotics are 5-HT<sub>1A</sub> receptor partial agonists, and this property has been shown to enhance their clinical efficacy.<ref name="pmid15189766"/><ref name="pmid10924666">{{cite journal | author = Rollema H, Lu Y, Schmidt AW, Sprouse JS, Zorn SH. | title = 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. | journal = Biol Psychiatry. | volume = 48 | issue = 3 | pages = 229–237 | year = 2000 | pmid = 10924666 | doi = 10.1016/S0006-3223(00)00850-7 }}</ref><ref name="pmid9456005">{{cite journal | author = Rollema H, Lu Y, Schmidt AW, Zorn SH. | title = Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation. | journal = Eur J Pharmacol. | volume = 338 | issue = 2 | pages = R3–5 | year = 1997 | pmid = 9456005 | doi = 10.1016/S0014-2999(97)81951-6 }}</ref> Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects seen upon postsynaptic activation of the 5-HT<sub>1A</sub> receptor.<ref name="pmid11792466">{{cite journal | author = Yoshino T, Nisijima K, Katoh S, Yui K, Nakamura M | title = Tandospirone potentiates the fluoxetine-induced increases in extracellular dopamine via 5-HT(1A) receptors in the rat medial frontal cortex | journal = Neurochemistry International | volume = 40 | issue = 4 | pages = 355–60 | year = 2002 | month = April | pmid = 11792466 | doi = 10.1016/S0197-0186(01)00079-1| url = http://linkinghub.elsevier.com/retrieve/pii/S0197018601000791}}</ref><ref name="pmid1681449">{{cite journal | author = Chojnacka-Wójcik E, Tatarczyńska E, Gołembiowska K, Przegaliński E | title = Involvement of 5-HT1A receptors in the antidepressant-like activity of gepirone in the forced swimming test in rats | journal = Neuropharmacology | volume = 30 | issue = 7 | pages = 711–7 | year = 1991 | month = July | pmid = 1681449 | doi = 10.1016/0028-3908(91)90178-E| url = }}</ref>
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Activation of 5-HT<sub>1A</sub> receptors has been demonstrated to impair [[cognition]], [[learning]], and [[memory]] by inhibiting the release of [[glutamate]] and [[acetylcholine]] in various areas of the [[brain]].<ref name="pmid18394726">{{cite journal | author = Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, Meister B, Kehr J, Stiedl O | title = The role of 5-HT(1A) receptors in learning and memory | journal = Behav Brain Res. | volume = 195 | issue = 1 | pages = 54–77 | year = 2008 | pmid = 18394726 | doi = 10.1016/j.bbr.2008.02.023 }}</ref> Conversely, 5-HT<sub>1A</sub> receptor [[antagonist]]s such as [[lecozotan]] have been shown to facilitate certain types of learning and memory in rodents, and as a result, are being developed as novel treatments for [[Alzheimer's disease]].<ref>{{cite journal | author = H. Spreitzer | date = August 13, 2008 | title = Neue Wirkstoffe - Lecozotan | journal = Österreichische Apothekerzeitung | issue = 17/2007 | pages = 805 | language = German }}</ref>
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Other effects of 5-HT<sub>1A</sub> activation include decreased [[aggression]] or increased serenic behavior,<ref name="pmid16310183">{{cite journal | author = de Boer SF, Koolhaas JM | title = 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis | journal = Eur J Pharmacol. | volume = 526 | issue = 1-3 | pages = 125–39 | year = 2005 | pmid = 18853336 | doi = 10.1016/j.ejphar.2005.09.065 }}</ref><ref name="pmid2091890">{{cite journal | author = Olivier B, Mos J, Rasmussen D. | title = Behavioural pharmacology of the serenic, eltoprazine | journal = Drug Metabol Drug Interact. | volume = 8 | issue = 1-2 | pages = 31–83 | year = 1990 | pmid = 2091890 }}</ref> increased [[sociability]],<ref name="pmid17383105">{{cite journal | author = Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS | title = A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy") | journal = Neuroscience | volume = 146 | issue = 2 | pages = 509–14 | year = 2007 | pmid = 17383105 | doi = 10.1016/j.neuroscience.2007.02.032 }}</ref> increased [[impulsivity]],<ref name="pmid15688093">{{cite journal | author = Winstanley CA, Theobald DE, Dalley JW, Robbins TW. | title = Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders. | journal = Neuropsychopharmacology. | volume = 30 | issue = 4 | pages = 669–682 | year = 2005 | pmid = 15688093 | doi = 10.1038/sj.npp.1300610 }}</ref> inhibition of [[addiction|addictive]] behavior,<ref name="pmid7862892">{{cite journal | author = Tomkins DM, Higgins GA, Sellers EM | title = Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake | journal = Psychopharmacology (Berl). | volume = 115 | issue = 1-2 | pages = 173–9 | year = 1994 | pmid = 7862892 | doi = 10.1007/BF02244769 }}</ref><ref name="pmid17316955">{{cite journal | author = Müller CP, Carey RJ, Huston JP, De Souza Silva MA | title = Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors | journal = Prog Neurobiol. | volume = 81 | issue = 3 | pages = 133–78 | year = 2007 | pmid = 17316955 | doi = 10.1016/j.pneurobio.2007.01.001 }}</ref><ref name="pmid15713268">{{cite journal | author = Carey RJ, DePalma G, Damianopoulos E, Shanahan A, Müller CP, Huston JP | title = Evidence that the 5-HT1A autoreceptor is an important pharmacological target for the modulation of cocaine behavioral stimulant effects | journal = Brain Res. | volume = 1034 | issue = 1-2 | pages = 162–71 | year = 2005 | pmid = 15713268 | doi = 10.1016/j.brainres.2004.12.012 }}</ref> facilitation of [[sexual behavior]] and [[sexual arousal|arousal]],<ref name="pmid8981617">{{cite journal | author = Fernández-Guasti A, Rodríguez-Manzo G | title = 8-OH-DPAT and male rat sexual behavior: partial blockade by noradrenergic lesion and sexual exhaustion | journal = Pharmacology, Biochemistry, and Behavior | volume = 56 | issue = 1 | pages = 111–6 | year = 1997 | month = January | pmid = 8981617 | doi = 10.1016/S0091-3057(96)00165-7 | url = }}</ref><ref name="pmid9228408">{{cite journal | author = Haensel SM, Slob AK | title = Flesinoxan: a prosexual drug for male rats | journal = European Journal of Pharmacology | volume = 330 | issue = 1 | pages = 1–9 | year = 1997 | month = July | pmid = 9228408 | doi = 10.1016/S0014-2999(97)00170-2| url = http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)00170-2}}</ref> inhibition of [[penile erection]],<ref name="pmid1357709">{{cite journal | author = Simon P, Guardiola B, Bizot-Espiard J, Schiavi P, Costentin J | title = 5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists | journal = Psychopharmacology | volume = 108 | issue = 1-2 | pages = 47–50 | year = 1992 | pmid = 1357709 | doi = 10.1007/BF02245284| url = }}</ref><ref name="pmid9085055">{{cite journal | author = Millan MJ, Perrin-Monneyron S | title = Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors | journal = Eur J Pharmacol. | volume = 321 | issue = 3 | pages = 11–3 | year = 1997 | pmid = 9085055 | doi = 10.1016/S0014-2999(97)00050-2 }}</ref> decreased food intake or [[Anorexia (symptom)|anorexia]],<ref name="pmid17609739">{{cite journal | author = Ebenezer IS, Arkle MJ, Tite RM | title = 8-Hydroxy-2-(di-n-propylamino)-tetralin inhibits food intake in fasted rats by an action at 5-HT1A receptors | journal = Methods Find Exp Clin Pharmacol. | volume = 29 | issue = 4 | pages = 269–72 | year = 1998 | pmid = 17609739 | doi = 10.1358/mf.2007.29.4.1075362 }}</ref> prolongation of [[Rapid eye movement sleep|REM]] [[sleep]] latency,<ref name="pmid10607047">{{cite journal | author = Monti JM, Jantos H | title = Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat | journal = J Sleep Res. | volume = 1 | issue = 3 | pages = 169–175 | year = 1992 | pmid = 10607047 | doi = 10.1111/j.1365-2869.1992.tb00033.x }}</ref><ref>{{cite journal | author = Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart | title = Pilot study of flesinoxan, a 5-HT1A agonist, in major depression: Effects on sleep REM latency and body temperature. | journal = Human Psychopharmacology: Clinical and Experimental | volume = 8 | issue = 4 | pages = 279–283 | year = 2004 | url = http://www3.interscience.wiley.com/journal/109710934/abstract | doi = 10.1002/hup.470080407 }}</ref> and enhanced [[breathing]] or [[hyperventilation]] and reversal of [[opioid]]-induced [[respiratory depression]].<ref name="pmid16166206">{{cite journal | author = Meyer LC, Fuller A, Mitchell D | title = Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 290 | issue = 2 | pages = R405–13 | year = 2006 | month = February | pmid = 16166206 | doi = 10.1152/ajpregu.00440.2005 | url = | issn = }}</ref>
  +
  +
=== Endocrinology ===
  +
  +
5-HT<sub>1A</sub> receptor activation induces the [[secretion]] of various [[hormone]]s including [[cortisol]], [[corticosterone]], [[adrenocorticotropic hormone]] (ACTH), [[oxytocin]], [[prolactin]], [[growth hormone]], and [[β-endorphin]].<ref name="pmid9678651">{{cite journal | author = Van de Kar LD, Levy AD, Li Q, Brownfield MS. | title = A comparison of the oxytocin and vasopressin responses to the 5-HT1A agonist and potential anxiolytic drug alnespirone (S-20499). | journal = Pharmacol Biochem Behav. | volume = 60 | issue = 3 |pages = 677–683 | year = 1998 | pmid = 9678651 | doi = 10.1016/S0091-3057(98)00025-2 }}</ref><ref name="pmid2952898">{{cite journal | author = Lorens SA, Van de Kar LD. | title = Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion. | journal = Neuroendocrinology. | volume = 45 | issue = 4 | pages = 305–310 | year = 1987 | pmid = 2952898 | doi = 10.1159/000124754 }}</ref><ref name="pmid2956114">{{cite journal | author = Koenig JI, Gudelsky GA, Meltzer HY. | title = Stimulation of corticosterone and beta-endorphin secretion in the rat by selective 5-HT receptor subtype activation. | journal = Eur J Pharmacol. | volume = 137 | issue = 1 | pages = 1–8 | year = 1987 | pmid = 2956114 | doi = 10.1016/0014-2999(87)90175-0 }}</ref><ref name="pmid15013031">{{cite journal | author = Pitchot W, Wauthy J, Legros JJ, Ansseau M | title = Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study | journal = European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology | volume = 14 | issue = 2 | pages = 151–5 | year = 2004 | month = March | pmid = 15013031 | doi = 10.1016/S0924-977X(03)00108-1 | url = }}</ref> The receptor does not affect [[vasopressin]] or [[renin]] secretion, unlike the [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s.<ref name="pmid9678651"/><ref name="pmid2952898"/> It has been suggested that oxytocin release may contribute to the prosocial, antiaggressive or serenic, and anxiolytic properties observed upon activation of the receptor.<ref name="pmid17383105"/> β-Endorphin secretion likely contributes to antidepressant, anxiolytic, and analgesic effects.
  +
  +
=== Autoreceptors ===
  +
  +
5-HT<sub>1A</sub> receptors can be located on the [[cell body]] or [[Soma (biology)|soma]], [[dendrite]]s, [[axon]]s, and both [[presynaptic]]ally and [[postsynaptic]]ally in [[nerve terminal]]s or [[synapse]]s. Those located on the soma and dendrites are called [[somatodendritic]], and those located presynaptically in the synapse are aptly titled presynaptic. As a group, they are known as [[autoreceptor]]s. Stimulation of 5-HT<sub>1A</sub> autoreceptors inhibits the release of serotonin in nerve terminals. For this reason, 5-HT<sub>1A</sub> receptor agonists tend to exert a biphasic mode of action; they decrease serotonin release and postsynaptic 5-HT<sub>1A</sub> receptor activity in low doses, and further decrease serotonin release but increase postsynaptic 5-HT<sub>1A</sub> receptor activity at moderate to high doses by directly stimulating the receptors in replacement of serotonin.
  +
  +
This autoreceptor-mediated inhibition of serotonin release has been postulated to be one of the reasons for the therapeutic lag that is commonly reported for most mainstream serotonergic antidepressants such as the SSRIs.<ref name="pmid10890313">{{cite journal | author = Hjorth S, Bengtsson HJ, Kullberg A, Carlzon D, Peilot H, Auerbach SB. | title = Serotonin autoreceptor function and antidepressant drug action. | journal = J Psychopharmacol. | volume = 14 | issue = 2 | pages = 177–185 | year = 2000 | pmid = 10890313 | doi = 10.1177/026988110001400208 }}</ref> The autoreceptors must first [[downregulation|densensitize]] before the concentration of extracellular serotonin in the synapse can become elevated appreciably.<ref name="pmid10890313"/><ref name="pmid8221701">{{cite journal | author = Briley M, Moret C. | title = Neurobiological mechanisms involved in antidepressant therapies. | journal = Clin Neuropharmacol. | volume = 16 | issue = 5 | pages = 387–400 | year = 1993 | pmid = 8221701 | doi = 10.1097/00002826-199310000-00002 }}</ref> Though the responsiveness of the autoreceptors is somewhat reduced with chronic treatment, they still remain effective at constraining large increases in extracellular serotonin concentrations.<ref name="pmid10890313"/> For this reason, [[serotonin reuptake inhibitor]]s that also have 5-HT<sub>1A</sub> receptor antagonistic properties such as [[SB-649915]] are currently being investigated as novel antidepressants with a faster onset of action and greater efficacy than many of those currently available.<ref name="pmid17356576">{{cite journal | author = Starr KR, Price GW, Watson JM, Atkinson PJ, Arban R, Melotto S, Dawson LA, Hagan JJ, Upton N, Duxon MS. | title = SB-649915-B, a novel 5-HT1A/B autoreceptor antagonist and serotonin reuptake inhibitor, is anxiolytic and displays fast onset activity in the rat high light social interaction test. | journal = Neuropsychopharmacology. | volume = 32 | issue = 10 | pages = 2163–2172| year = 2007 | pmid = 17356576 | doi = 10.1038/sj.npp.1301341 }}</ref>
  +
  +
Unlike most drugs that elevate extracellular serotonin levels like the SSRIs and MAOIs, SRAs such as [[fenfluramine]] and [[MDMA]] ("Ecstasy") fully bypass serotonin autoreceptors like 5-HT<sub>1A</sub> by forcing release to occur regardless of their inhibition.<ref name="pmid17017961">{{cite journal | author = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–59 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766| url = http://www.bentham-direct.org/pages/content.php?CTMC/2006/00000006/00000017/0004R.SGM}}</ref> This is why SRAs display immediate and full effects in contrast to drugs like the SSRIs, which require several weeks of chronic dosing before therapeutic benefits are seen, and also why SRAs are much stronger than SSRIs and related compounds in effect as they produce far more robust and balanced increases in extracellular serotonin concentrations.<ref name="pmid10428424">{{cite journal | author = Scorza C, Silveira R, Nichols DE, Reyes-Parada M | title = Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action | journal = Neuropharmacology | volume = 38 | issue = 7 | pages = 1055–61 | year = 1999 | month = July | pmid = 10428424 | doi = 10.1016/S0028-3908(99)00023-4| url = http://linkinghub.elsevier.com/retrieve/pii/S0028390899000234}}</ref><ref name="pmid9694528">{{cite journal | author = Marona-Lewicka D, Nichols DE | title = Drug discrimination studies of the interoceptive cues produced by selective serotonin uptake inhibitors and selective serotonin releasing agents | journal = Psychopharmacology | volume = 138 | issue = 1 | pages = 67–75 | year = 1998 | month = July | pmid = 9694528 | doi = 10.1007/s002130050646| url = http://link.springer.de/link/service/journals/00213/bibs/8138001/81380067.htm}}</ref> For these reasons, [[selective serotonin releasing agent]]s (SSRAs) including [[MDAI]], [[MMAI]], and [[4-Methylthioamphetamine|4-MTA]] have been proposed as novel antidepressants with an immediate onset of action and far greater efficacy in comparison to most current treatments.<ref name="pmid10428424"/>
  +
  +
Sufficient doses of 5-HT<sub>1A</sub> receptor agonists themselves, like SRAs, are capable of fully bypassing the 5-HT<sub>1A</sub> autoreceptor-mediated inhibition of serotonin release and therefore decreased 5-HT<sub>1A</sub> postsynaptic receptor activation as well, by directly agonizing the postsynaptic receptors [[in lieu]] of serotonin. It is mentionable, however, that, unlike SRAs, 5-HT<sub>1A</sub> receptor agonists are incapable of bypassing the inhibitory effect of 5-HT<sub>1A</sub> autoreceptors located as [[heteroreceptor]]s in non-[[serotonergic]] [[synapse]]s where 5-HT<sub>1A</sub> postsynaptic receptors are not present, which, instead of serotonin, modulate the release of other [[neurotransmitter]]s such as [[dopamine]] or [[glutamate]].
  +
  +
== Ligands ==
  +
  +
The distribution of 5-HT<sub>1A</sub> receptors in the [[human brain]] may be imaged with the [[positron emission tomography]] using the [[radioligand]] [<sup>11</sup>C][[WAY-100,635]].<ref name="pmid7498295">{{cite journal | author = Pike VW, McCarron JA, Lammerstma AA, Hume SP, Poole K, Grasby PM, Malizia A, Cliffe IA, Fletcher A, Bench CJ | title = First delineation of 5-HT<sub>1A</sub> receptors in human brain with PET and [<sup>11</sup>C]WAY-100635 | journal = Eur. J. Pharmacol. | volume = 283 | issue = 1-3 | pages = R1–3 | year = 1995 | pmid = 7498295 | doi = 10.1016/0014-2999(95)00438-Q }}</ref>
  +
For example, one study has found increased 5-HT<sub>1A</sub> binding in type 2 [[diabetes]].<ref name="pmid11814436">{{cite journal | author = Price JC, Kelley DE, Ryan CM, Meltzer CC, Drevets WC, Mathis CA, Mazumdar S, Reynolds CF | title = Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study | journal = Brain Res. | volume = 927 | issue = 1 | pages = 97–103 | year = 2002 | pmid = 11814436 | doi = 10.1016/S0006-8993(01)03297-8 }}</ref> Another PET study found a negative correlation between the amount of 5-HT<sub>1A</sub> binding in the [[raphe nuclei]], [[hippocampus]] and [[neocortex]] and a self-reported tendency to have [[spiritual experience]]s.<ref name="pmid14594742">{{cite journal | author = Borg J, Andrée B, Soderstrom H, Farde L | title = The serotonin system and spiritual experiences | journal = Am J Psychiatry | volume = 160 | issue = 11 | pages = 1965–9 | year = 2003 | month = November | pmid = 14594742 | doi = 10.1176/appi.ajp.160.11.1965 | url = }}</ref> Labeled with [[tritium]], WAY-100,635 may also be used in [[autoradiography]].<ref name="pmid9152998">{{cite journal | author = Burnet PW, Eastwood SL, Harrison PJ | title = [<sup>3</sup>H]WAY-100635 for 5-HT<sub>1A</sub> receptor autoradiography in human brain: a comparison with [<sup>3</sup>H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia | journal = Neurochem. Int. | volume = 30 | issue = 6 | pages = 565–574 | year = 1997 | pmid = 9152998 | doi = 10.1016/S0197-0186(96)00124-6}}</ref>
  +
  +
=== Agonists ===
  +
  +
<div style="-moz-column-count:5; column-count:5; -webkit-column-count:5;">
  +
  +
* [[5-Carboxamidotryptamine|5-CT]]
  +
* [[5-MeO-DMT]]
  +
* [[5-Methoxytryptamine|5-MT]]
  +
* [[8-OH-DPAT]]
  +
* [[Adatanserin]]
  +
* [[alpha-Ethyltryptamine|αET]]
  +
* [[Alnespirone]]
  +
* [[alpha-Methyltryptamine|αMT]]
  +
* [[Aripiprazole]]
  +
* [[Asenapine]]
  +
* [[Befiradol]]
  +
* [[Binospirone]]
  +
* [[Bufotenin]]
  +
* [[Buspirone]]
  +
* [[Cannabidiol]]
  +
* [[Clozapine]]
  +
* [[Dihydroergotamine]]
  +
* [[Dimethyltryptamine|DMT]]
  +
* [[Ebalzotan]]
  +
* [[Eltoprazine]]
  +
* [[Eptapirone]]
  +
* [[Ergotamine]]
  +
* [[Etoperidone]]
  +
* [[F-11,461]]
  +
* [[F-12,826]]
  +
* [[F-13,714]]
  +
* [[F-14,679]]
  +
* [[F-15,599]]
  +
* [[Flesinoxan]]
  +
* [[Flibanserin]]
  +
* [[Gepirone]]
  +
* [[Ipsapirone]]
  +
* [[Lesopitron]]
  +
* [[Lysergic acid diethylamide|LSD]]
  +
* [[Lu AA21004]]
  +
* [[LY-293,284]]
  +
* [[LY-301,317]]
  +
* [[MDMA]]
  +
* [[Methysergide]]
  +
* [[MKC-242]]
  +
* [[NBUMP]]
  +
* [[Nefazodone]]
  +
* [[Osemozotan]]
  +
* [[Perospirone]]
  +
* [[Piclozotan]]
  +
* [[Psilocin]]
  +
* [[Psilocybin]]
  +
* [[PRX-00023]]
  +
* [[Rauwolscine]]
  +
* [[Repinotan]]
  +
* [[RU-24,969]]
  +
* [[S-15,535]]
  +
* [[Sarizotan]]
  +
* [[SSR-181,507]]
  +
* [[Sunepitron]]
  +
* [[Tandospirone]]
  +
* [[Tiospirone]]
  +
* [[Trazodone]]
  +
* [[U-92,016-A]]
  +
* [[Urapidil]]
  +
* [[Vilazodone]]
  +
* [[Yohimbine]]
  +
* [[Xaliproden]]
  +
* [[Zalospirone]]
  +
* [[Ziprasidone]]
  +
  +
</div>
  +
  +
=== Antagonists ===
  +
  +
<div style="-moz-column-count:5; column-count:5; -webkit-column-count:5;">
  +
  +
* [[Alprenolol]]
  +
* [[AV-965]]
  +
* [[BMY-7,378]]
  +
* [[Cyanopindolol]]
  +
* [[Dotarizine]]
  +
* [[Flopropione]]
  +
* [[GR-46,611]]
  +
* [[Iodocyanopindolol]]
  +
* [[Isamoltane]]
  +
* [[Lecozotan]]
  +
* [[Methiothepin]]
  +
* [[MPPF]]
  +
* [[NAN-190]]
  +
* [[Oxprenolol]]
  +
* [[Pindobind]]
  +
* [[Pindolol]]
  +
* [[Quetiapine]]
  +
* [[Robalzotan]]
  +
* [[SB-649,915]]
  +
* [[SDZ-216,525]]
  +
* [[Spiperone]]
  +
* [[Spiramide]]
  +
* [[Spiroxatrine]]
  +
* [[UH-301]]
  +
* [[WAY-100,135]]
  +
* [[WAY-100,635]]
  +
* [[Xylamidine]]
  +
  +
</div>
  +
  +
== Genetics ==
  +
  +
The 5-HT<sub>1A</sub> receptor is coded by the ''HTR1A'' [[gene]]. There are several human [[Polymorphism (biology)|polymorphism]]s associated with this gene. A 2007 review listed 27 [[single nucleotide polymorphism]]s (SNP).<ref name="pmid18047755">{{cite journal | author = Drago A, Ronchi DD, Serretti A | title = 5-HT<sub>1A</sub> gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies | journal = Int. J. Neuropsychopharmacol. | volume = 11 | issue = 5 | pages = 701–21 | year = 2008 | month = August | pmid = 18047755 | doi = 10.1017/S1461145707008218 | url = }}</ref> The most investigated SNPs are C-1019G ([[rs6295]]), C-1018G,<ref name="pmid10412191">{{cite journal | author = Wu S, Comings DE | title = A common C-1018G polymorphism in the human 5-HT<sub>1A</sub> receptor gene | journal = Psychiatr. Genet. | volume = 9 | issue = 2 | pages = 105–6 | year = 1999 | month = June | pmid = 10412191 | url = | doi = 10.1097/00041444-199906000-00010 }}</ref> Ile28Val ([[rs1799921]]), Arg219Leu ([[rs1800044]]), and Gly22Ser ([[rs1799920]]).<ref name="pmid18047755">{{cite journal | author = Drago A, Ronchi DD, Serretti A | title = 5-HT<sub>1A</sub> gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies | journal = Int. J. Neuropsychopharmacol. | volume = 11 | issue = 5 | pages = 701–21 | year = 2008 | month = August | pmid = 18047755 | doi = 10.1017/S1461145707008218 | url = }}</ref> Some of the other SNPs are Pro16Leu, Gly272Asp, and the [[synonymous polymorphism]] G294A ([[rs6294]]). These gene variants have been studied in relation to [[psychiatric disorder]]s with no definitive results.<ref name="pmid18047755">{{cite journal | author = Drago A, Ronchi DD, Serretti A | title = 5-HT<sub>1A</sub> gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies | journal = Int. J. Neuropsychopharmacol. | volume = 11 | issue = 5 | pages = 701–21 | year = 2008 | month = August | pmid = 18047755 | doi = 10.1017/S1461145707008218 | url = }}</ref>
  +
  +
== Interactions ==
  +
  +
The 5-HT<sub>1A</sub> receptor has been shown to [[protein-protein interaction|interact]] with [[brain-derived neurotrophic factor]] (BDNF), which may play a major role in its regulation of mood and anxiety.<ref name="pmid17401528">{{cite journal | author = Anttila S, Huuhka K, Huuhka M, Rontu R, Hurme M, Leinonen E et al. | title = Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression. | journal = J Neural Transm | year = 2007 | volume = 114 | issue = 8 | pages = 1065–8 | pmid = 17401528
  +
| url = http://www.ncbi.nlm.nih.gov/pubmed/17401528 | doi = 10.1007/s00702-007-0705-9 }}</ref><ref name="pmid17559709">{{cite journal| author=Guiard BP, David DJ, Deltheil T, Chenu F, Le Maître E, Renoir T et al.| title=Brain-derived neurotrophic factor-deficient mice exhibit a hippocampal hyperserotonergic phenotype. | journal=Int J Neuropsychopharmacol | year= 2008 | volume= 11 | issue= 1 | pages= 79–92 | pmid=17559709 | doi=10.1017/S1461145707007857 }}</ref> It has also been shown to interact with [[sphingosine-1-phosphate receptor 1]] (S1PR<sub>1</sub>).<ref name=pmid11854302>{{cite journal | quotes = yes |last=Salim |first=Kamran |authorlink= |coauthors=Fenton Tim, Bacha Jamil, Urien-Rodriguez Hector, Bonnert Tim, Skynner Heather A, Watts Emma, Kerby Julie, Heald Anne, Beer Margaret, McAllister George, Guest Paul C |year=[[2002]]|month=May. |title=Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation |journal=J. Biol. Chem. |volume=277 |issue=18 |pages=15482–5 |publisher= |location = United States| issn = 0021-9258| pmid = 11854302 |doi = 10.1074/jbc.M201539200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>
  +
  +
== See also ==
  +
* [[5-HT receptor]]
  +
* [[5-HT1 receptor|5-HT<sub>1</sub> receptor]]
  +
  +
== References ==
  +
{{Reflist|2}}
  +
  +
== Further reading ==
  +
{{Refbegin|2}}
  +
{{PBB_Further_reading
  +
| citations =
  +
* {{cite journal | author=el Mestikawy S, Fargin A, Raymond JR, ''et al.'' |title=The 5-HT1A receptor: an overview of recent advances |journal=Neurochem. Res. |volume=16 |issue= 1 |pages= 1–10 |year= 1991 |pmid= 2052135 |doi=10.1007/BF00965820 }}
  +
* {{cite journal | author=Hensler JG |title=Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration |journal=Life Sci. |volume=72 |issue= 15 |pages= 1665–82 |year= 2003 |pmid= 12559389 |doi=10.1016/S0024-3205(02)02482-7 }}
  +
* {{cite journal | author=Van Oekelen D, Luyten WH, Leysen JE |title=5-HT2A and 5-HT2C receptors and their atypical regulation properties |journal=Life Sci. |volume=72 |issue= 22 |pages= 2429–49 |year= 2003 |pmid= 12650852 |doi=10.1016/S0024-3205(03)00141-3 }}
  +
* {{cite journal | author=Lesch KP, Gutknecht L |title=Focus on The 5-HT1A receptor: emerging role of a gene regulatory variant in psychopathology and pharmacogenetics |journal=Int. J. Neuropsychopharmacol. |volume=7 |issue= 4 |pages= 381–5 |year= 2005 |pmid= 15683551 |doi= 10.1017/S1461145704004845 }}
  +
* {{cite journal | author=Kalipatnapu S, Chattopadhyay A |title=Membrane protein solubilization: recent advances and challenges in solubilization of serotonin1A receptors |journal=IUBMB Life |volume=57 |issue= 7 |pages= 505–12 |year= 2006 |pmid= 16081372 |doi= 10.1080/15216540500167237 }}
  +
* {{cite journal | author=Varrault A, Bockaert J, Waeber C |title=Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis |journal=Mol. Biol. Cell |volume=3 |issue= 9 |pages= 961–9 |year= 1992 |pmid= 1330092 |doi= | pmc=275657 }}
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* {{cite journal | author=Levy FO, Gudermann T, Perez-Reyes E, ''et al.'' |title=Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype |journal=J. Biol. Chem. |volume=267 |issue= 11 |pages= 7553–62 |year= 1992 |pmid= 1559993 |doi= }}
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* {{cite journal | author=Melmer G, Sherrington R, Mankoo B, ''et al.'' |title=A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to dna loci D5S6, D5S39, and D5S76 |journal=Genomics |volume=11 |issue= 3 |pages= 767–9 |year= 1992 |pmid= 1685484 |doi=10.1016/0888-7543(91)90088-V }}
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* {{cite journal | author=Parks CL, Chang LS, Shenk T |title=A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region |journal=Nucleic Acids Res. |volume=19 |issue= 25 |pages= 7155–60 |year= 1992 |pmid= 1766875 |doi=10.1093/nar/19.25.7155 | pmc=332551 }}
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* {{cite journal | author=Gilliam TC, Freimer NB, Kaufmann CA, ''et al.'' |title=Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia |journal=Genomics |volume=5 |issue= 4 |pages= 940–4 |year= 1990 |pmid= 2591972 |doi=10.1016/0888-7543(89)90138-9 }}
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* {{cite journal | author=Kobilka BK, Frielle T, Collins S, ''et al.'' |title=An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins |journal=Nature |volume=329 |issue= 6134 |pages= 75–9 |year= 1987 |pmid= 3041227 |doi= 10.1038/329075a0 }}
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* {{cite journal | author=Fargin A, Raymond JR, Lohse MJ, ''et al.'' |title=The genomic clone G-21, which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor |journal=Nature |volume=335 |issue= 6188 |pages= 358–60 |year= 1988 |pmid= 3138543 |doi= 10.1038/335358a0 }}
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* {{cite journal | author=Nakhai B, Nielsen DA, Linnoila M, Goldman D |title=Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28 |journal=Biochem. Biophys. Res. Commun. |volume=210 |issue= 2 |pages= 530–6 |year= 1995 |pmid= 7755630 |doi=10.1006/bbrc.1995.1692 }}
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* {{cite journal | author=Aune TM, McGrath KM, Sarr T, ''et al.'' |title=Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine |journal=J. Immunol. |volume=151 |issue= 3 |pages= 1175–83 |year= 1993 |pmid= 8393041 |doi= }}
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* {{cite journal | author=Parks CL, Shenk T |title=The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1 |journal=J. Biol. Chem. |volume=271 |issue= 8 |pages= 4417–30 |year= 1996 |pmid= 8626793 |doi=10.1074/jbc.271.8.4417 }}
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* {{cite journal | author=Stockmeier CA, Shapiro LA, Dilley GE, ''et al.'' |title=Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity |journal=J. Neurosci. |volume=18 |issue= 18 |pages= 7394–401 |year= 1998 |pmid= 9736659 |doi= }}
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* {{cite journal | author=Kawanishi Y, Harada S, Tachikawa H, ''et al.'' |title=Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia |journal=Am. J. Med. Genet. |volume=81 |issue= 5 |pages= 434–9 |year= 1998 |pmid= 9754630 |doi=10.1002/(SICI)1096-8628(19980907)81:5<434::AID-AJMG13>3.0.CO;2-D }}
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* {{cite journal | author=Salim K, Fenton T, Bacha J, ''et al.'' |title=Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation |journal=J. Biol. Chem. |volume=277 |issue= 18 |pages= 15482–5 |year= 2002 |pmid= 11854302 |doi= 10.1074/jbc.M201539200 }}
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}}
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== External links ==
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* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2310 | title = 5-HT<sub>1A</sub> | accessdate = | author = | authorlink = | coauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
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{{G protein-coupled receptors}}
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{{Serotonergics}}
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[[Category:G protein coupled receptors]]

Latest revision as of 16:03, 29 March 2010

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The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gi/Go and mediates inhibitory neurotransmission. HTR1A denotes the human gene encoding for the receptor.[1][2]

Distribution

The 5-HT1A receptor is the most widespread of all the 5-HT receptors. In the central nervous system, 5-HT1A receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and raphe nucelus in high densities, while low amounts also exist in the basal ganglia and thalamus.[3][4][5] The 5-HT1A receptors in the raphe nucleus are largely somatodendritic autoreceptors.[4]

Function

Neuromodulation

5-HT1A receptor agonists decrease blood pressure and heart rate or cause hypotension via a central mechanism, by inducing peripheral vasodilation, and by stimulating the vagus nerve.[6] These effects are the result of activation of 5-HT1A receptors within the rostral ventrolateral medulla.[6] The sympatholytic antihypertensive drug urapidil is an α1-adrenergic receptor antagonist and α2-adrenergic receptor agonist, as well as 5-HT1A receptor agonist, and it has been demonstrated that the latter property contributes to its overall therapeutic effects.[7][8]

Vasodilation of the blood vessels in the skin via central 5-HT1A activation increases heat dissipation from the organism out into the environment, causing a decrease in body temperature or hypothermia.[9][10]

Activation of central 5-HT1A receptors triggers the release or inhibition of norepinephrine depending on species, presumably from the locus coeruleus, which then reduces or increases neuronal tone to the iris sphincter muscle by modulation of postsynaptic α2-adrenergic receptors within the Edinger-Westphal nucleus, resulting in pupil dilation or mydriasis in rodents, and pupil constriction or miosis in primates like humans.[11][12][13]

5-HT1A receptor agonists like buspirone[14] and flesinoxan[15] show efficacy in relieving anxiety[16] and depression,[17] and buspirone and tandospirone are currently approved for these indications in various parts of the world. Others such as gepirone,[18] flesinoxan,[15] flibanserin,[19] and PRX-00023[20] have also been investigated, though none have been fully developed and approved as of yet. Some of the atypical antipsychotics like aripiprazole[21] are also partial agonists at the 5-HT1A receptor and are often used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs).[22]

5-HT1A autoreceptor desensitization and increased 5-HT1A receptor postsynaptic activation via general increases in serotonin levels by serotonin precursor supplementation, serotonin reuptake inhibition, or monoamine oxidase inhibition has been shown to be a major mediator in the therapeutic benefits of most mainstream antidepressant supplements and pharmaceuticals, including serotonin precursors like L-tryptophan and 5-HTP, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), and monoamine oxidase inhibitors (MAOIs).[23] 5-HT1A receptor activation likely plays a significant role in the positive effects of serotonin releasing agents (SRAs) like MDMA ("Ecstasy") as well.[24][25]

5-HT1A receptors in the dorsal raphe nucleus are co-localized with neurokinin 1 (NK1) receptors and have been shown to inhibit the release of substance P, their endogenous ligand.[26][27] In addition to being antidepressant and anxiolytic in effect, 5-HT1A receptor activation has also been demonstrated to be antiemetic[28][29] and analgesic,[30][31] and all of these properties may be mediated in part or full, depending on the property in question, by NK1 receptor inhibition. Consequently, novel NK1 receptor antagonists are now in use for the treatment of nausea and emesis, and are also being investigated for the treatment of anxiety and depression.[32]

5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus, and may be useful for improving the symptoms of schizophrenia and Parkinson's disease.[33][34] As mentioned above, some of the atypical antipsychotics are 5-HT1A receptor partial agonists, and this property has been shown to enhance their clinical efficacy.[33][35][36] Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects seen upon postsynaptic activation of the 5-HT1A receptor.[37][38]

Activation of 5-HT1A receptors has been demonstrated to impair cognition, learning, and memory by inhibiting the release of glutamate and acetylcholine in various areas of the brain.[39] Conversely, 5-HT1A receptor antagonists such as lecozotan have been shown to facilitate certain types of learning and memory in rodents, and as a result, are being developed as novel treatments for Alzheimer's disease.[40]

Other effects of 5-HT1A activation include decreased aggression or increased serenic behavior,[41][42] increased sociability,[25] increased impulsivity,[43] inhibition of addictive behavior,[44][45][46] facilitation of sexual behavior and arousal,[47][48] inhibition of penile erection,[49][50] decreased food intake or anorexia,[51] prolongation of REM sleep latency,[52][53] and enhanced breathing or hyperventilation and reversal of opioid-induced respiratory depression.[54]

Endocrinology

5-HT1A receptor activation induces the secretion of various hormones including cortisol, corticosterone, adrenocorticotropic hormone (ACTH), oxytocin, prolactin, growth hormone, and β-endorphin.[55][56][57][58] The receptor does not affect vasopressin or renin secretion, unlike the 5-HT2 receptors.[55][56] It has been suggested that oxytocin release may contribute to the prosocial, antiaggressive or serenic, and anxiolytic properties observed upon activation of the receptor.[25] β-Endorphin secretion likely contributes to antidepressant, anxiolytic, and analgesic effects.

Autoreceptors

5-HT1A receptors can be located on the cell body or soma, dendrites, axons, and both presynaptically and postsynaptically in nerve terminals or synapses. Those located on the soma and dendrites are called somatodendritic, and those located presynaptically in the synapse are aptly titled presynaptic. As a group, they are known as autoreceptors. Stimulation of 5-HT1A autoreceptors inhibits the release of serotonin in nerve terminals. For this reason, 5-HT1A receptor agonists tend to exert a biphasic mode of action; they decrease serotonin release and postsynaptic 5-HT1A receptor activity in low doses, and further decrease serotonin release but increase postsynaptic 5-HT1A receptor activity at moderate to high doses by directly stimulating the receptors in replacement of serotonin.

This autoreceptor-mediated inhibition of serotonin release has been postulated to be one of the reasons for the therapeutic lag that is commonly reported for most mainstream serotonergic antidepressants such as the SSRIs.[59] The autoreceptors must first densensitize before the concentration of extracellular serotonin in the synapse can become elevated appreciably.[59][60] Though the responsiveness of the autoreceptors is somewhat reduced with chronic treatment, they still remain effective at constraining large increases in extracellular serotonin concentrations.[59] For this reason, serotonin reuptake inhibitors that also have 5-HT1A receptor antagonistic properties such as SB-649915 are currently being investigated as novel antidepressants with a faster onset of action and greater efficacy than many of those currently available.[61]

Unlike most drugs that elevate extracellular serotonin levels like the SSRIs and MAOIs, SRAs such as fenfluramine and MDMA ("Ecstasy") fully bypass serotonin autoreceptors like 5-HT1A by forcing release to occur regardless of their inhibition.[62] This is why SRAs display immediate and full effects in contrast to drugs like the SSRIs, which require several weeks of chronic dosing before therapeutic benefits are seen, and also why SRAs are much stronger than SSRIs and related compounds in effect as they produce far more robust and balanced increases in extracellular serotonin concentrations.[63][64] For these reasons, selective serotonin releasing agents (SSRAs) including MDAI, MMAI, and 4-MTA have been proposed as novel antidepressants with an immediate onset of action and far greater efficacy in comparison to most current treatments.[63]

Sufficient doses of 5-HT1A receptor agonists themselves, like SRAs, are capable of fully bypassing the 5-HT1A autoreceptor-mediated inhibition of serotonin release and therefore decreased 5-HT1A postsynaptic receptor activation as well, by directly agonizing the postsynaptic receptors in lieu of serotonin. It is mentionable, however, that, unlike SRAs, 5-HT1A receptor agonists are incapable of bypassing the inhibitory effect of 5-HT1A autoreceptors located as heteroreceptors in non-serotonergic synapses where 5-HT1A postsynaptic receptors are not present, which, instead of serotonin, modulate the release of other neurotransmitters such as dopamine or glutamate.

Ligands

The distribution of 5-HT1A receptors in the human brain may be imaged with the positron emission tomography using the radioligand [11C]WAY-100,635.[65] For example, one study has found increased 5-HT1A binding in type 2 diabetes.[66] Another PET study found a negative correlation between the amount of 5-HT1A binding in the raphe nuclei, hippocampus and neocortex and a self-reported tendency to have spiritual experiences.[67] Labeled with tritium, WAY-100,635 may also be used in autoradiography.[68]

Agonists

Antagonists

  • Alprenolol
  • AV-965
  • BMY-7,378
  • Cyanopindolol
  • Dotarizine
  • Flopropione
  • GR-46,611
  • Iodocyanopindolol
  • Isamoltane
  • Lecozotan
  • Methiothepin
  • MPPF
  • NAN-190
  • Oxprenolol
  • Pindobind
  • Pindolol
  • Quetiapine
  • Robalzotan
  • SB-649,915
  • SDZ-216,525
  • Spiperone
  • Spiramide
  • Spiroxatrine
  • UH-301
  • WAY-100,135
  • WAY-100,635
  • Xylamidine

Genetics

The 5-HT1A receptor is coded by the HTR1A gene. There are several human polymorphisms associated with this gene. A 2007 review listed 27 single nucleotide polymorphisms (SNP).[69] The most investigated SNPs are C-1019G (rs6295), C-1018G,[70] Ile28Val (rs1799921), Arg219Leu (rs1800044), and Gly22Ser (rs1799920).[69] Some of the other SNPs are Pro16Leu, Gly272Asp, and the synonymous polymorphism G294A (rs6294). These gene variants have been studied in relation to psychiatric disorders with no definitive results.[69]

Interactions

The 5-HT1A receptor has been shown to interact with brain-derived neurotrophic factor (BDNF), which may play a major role in its regulation of mood and anxiety.[71][72] It has also been shown to interact with sphingosine-1-phosphate receptor 1 (S1PR1).[73]

See also

References

  1. ↑ Gilliam TC, Freimer NB, Kaufmann CA, Powchik PP, Bassett AS, Bengtsson U, Wasmuth JJ (November 1989). Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia. Genomics 5 (4): 940–4.
  2. ↑ Entrez Gene: HTR1A 5-hydroxytryptamine (serotonin) receptor 1A.
  3. ↑ Ito H, Halldin C, Farde L. (1999). Localization of 5-HT1A receptors in the living human brain using [carbonyl-11C]WAY-100635: PET with anatomic standardization technique.. J Nucl Med. 40 (1): 102–109.
  4. ↑ 4.0 4.1 Glennon RA, Dukat M, Westkaemper RB. Serotonin Receptor Subtypes and Ligands. American College of Neurophyscopharmacology. URL accessed on 2008-04-11.
  5. ↑ de Almeida J, Mengod G. (2008). Serotonin 1A receptors in human and monkey prefrontal cortex are mainly expressed in pyramidal neurons and in a GABAergic interneuron subpopulation: implications for schizophrenia and its treatment.. J Neurochem. 107 (2): 488–496.
  6. ↑ 6.0 6.1 Dabiré H. (1991). Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation.. Therapie. 46 (6): 421–9.
  7. ↑ Ramage AG (April 1991). The mechanism of the sympathoinhibitory action of urapidil: role of 5-HT1A receptors. Br. J. Pharmacol. 102 (4): 998–1002.
  8. ↑ Kolassa N, Beller KD, Sanders KH. (1989). Involvement of brain 5-HT1A receptors in the hypotensive response to urapidil.. Am J Cardiol. 64 (7): 7D–10D.
  9. ↑ Ootsuka Y, Blessing WW. (2006). Activation of 5-HT1A receptors in rostral medullary raphé inhibits cutaneous vasoconstriction elicited by cold exposure in rabbits.. Brain Res. 1073-1074: 252–61.
  10. ↑ Rusyniak DE, Zaretskaia MV, Zaretsky DV, DiMicco JA. (2007). 3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors.. J Pharmacol Exp Ther. 323 (2): 477–487.
  11. ↑ Yu Y, Ramage AG, Koss MC. (2004). Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats.. Eur J Pharmacol. 489 (3): 207–213.
  12. ↑ Prow MR, Martin KF, Heal DJ (1996). 8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation. Eur J Pharmacol. 317 (1): 21–8.
  13. ↑ Fanciullacci M, Sicuteri R, Alessandri M, Geppetti P (March 1995). Buspirone, but not sumatriptan, induces miosis in humans: relevance for a serotoninergic pupil control. Clinical Pharmacology and Therapeutics 57 (3): 349–55.
  14. ↑ Cohn, JB, Rickels K (1989). A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety. Curr Med Res Opin. 11 (5): 304–320.
  15. ↑ 15.0 15.1 Cryan JF, Redmond AM, Kelly JP, Leonard BE. (1997). The effects of the 5-HT1A agonist flesinoxan, in three paradigms for assessing antidepressant potential in the rat.. Eur Neuropsychopharmacol. 7 (2): 109–114. Cite error: Invalid <ref> tag; name "pmid9169298" defined multiple times with different content
  16. ↑ Parks CL, Robinson PS, Sibille E, Shenk T, Toth M (1998). Increased anxiety of mice lacking the serotonin1A receptor. Proc Natl Acad Sci U S A. 195 (18): 10734–9.
  17. ↑ Kennett GA, Dourish CT, Curzon G (1987). Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol. 134 (3): 265–74.
  18. ↑ Keller MB, Ruwe FJ, Janssens CJ, Sitsen JM, Jokinen R, Janczewski J (February 2005). Relapse prevention with gepirone ER in outpatients with major depression. Journal of Clinical Psychopharmacology 25 (1): 79–84.
  19. ↑ Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R (August 2003). Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors.. Br J Pharmacol. 139 (7): 1281–8.
  20. ↑ de Paulis T. (2007). Drug evaluation: PRX-00023, a selective 5-HT1A receptor agonist for depression.. Curr Opin Investig Drugs. 8 (1): 78–86.
  21. ↑ Stark, AD et al. (2007). Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies.. Psychopharmacology (Berl) 190 (3): 373–382.
  22. ↑ Vega, JAW, Mortimer AM, Tyson PJ (May 2003). Conventional Antipsychotic Prescription in Unipolar Depression, I: An Audit and Recommendations for Practice. The Journal of Clinical Psychiatry 64 (5): 568–574.
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  25. ↑ 25.0 25.1 25.2 Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS (May 2007). A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy"). Neuroscience 146 (2): 509–14. Cite error: Invalid <ref> tag; name "pmid17383105" defined multiple times with different content
  26. ↑ Gobbi G, Cassano T, Radja F, Morgese MG, Cuomo V, Santarelli L, Hen R, Blier P (April 2007). Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 17 (5): 328–38.
  27. ↑ Baker KG, Halliday GM, Hornung J-P, Geffen LB, Cotton RGH, Tork I. Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus. Neuroscience. 1991;42(3):757-75.
  28. ↑ Lucot JB (February 1994). Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin. European Journal of Pharmacology 253 (1-2): 53–60.
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  44. ↑ Tomkins DM, Higgins GA, Sellers EM (1994). Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake. Psychopharmacology (Berl). 115 (1-2): 173–9.
  45. ↑ Müller CP, Carey RJ, Huston JP, De Souza Silva MA (2007). Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Prog Neurobiol. 81 (3): 133–78.
  46. ↑ Carey RJ, DePalma G, Damianopoulos E, Shanahan A, Müller CP, Huston JP (2005). Evidence that the 5-HT1A autoreceptor is an important pharmacological target for the modulation of cocaine behavioral stimulant effects. Brain Res. 1034 (1-2): 162–71.
  47. ↑ Fernández-Guasti A, Rodríguez-Manzo G (January 1997). 8-OH-DPAT and male rat sexual behavior: partial blockade by noradrenergic lesion and sexual exhaustion. Pharmacology, Biochemistry, and Behavior 56 (1): 111–6.
  48. ↑ Haensel SM, Slob AK (July 1997). Flesinoxan: a prosexual drug for male rats. European Journal of Pharmacology 330 (1): 1–9.
  49. ↑ Simon P, Guardiola B, Bizot-Espiard J, Schiavi P, Costentin J (1992). 5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists. Psychopharmacology 108 (1-2): 47–50.
  50. ↑ Millan MJ, Perrin-Monneyron S (1997). Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors. Eur J Pharmacol. 321 (3): 11–3.
  51. ↑ Ebenezer IS, Arkle MJ, Tite RM (1998). 8-Hydroxy-2-(di-n-propylamino)-tetralin inhibits food intake in fasted rats by an action at 5-HT1A receptors. Methods Find Exp Clin Pharmacol. 29 (4): 269–72.
  52. ↑ Monti JM, Jantos H (1992). Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat. J Sleep Res. 1 (3): 169–175.
  53. ↑ Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart (2004). Pilot study of flesinoxan, a 5-HT1A agonist, in major depression: Effects on sleep REM latency and body temperature.. Human Psychopharmacology: Clinical and Experimental 8 (4): 279–283.
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  73. ↑ Salim, Kamran, Fenton Tim, Bacha Jamil, Urien-Rodriguez Hector, Bonnert Tim, Skynner Heather A, Watts Emma, Kerby Julie, Heald Anne, Beer Margaret, McAllister George, Guest Paul C (May. 2002). Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation. J. Biol. Chem. 277 (18): 15482–5.

Further reading


  • el Mestikawy S, Fargin A, Raymond JR, et al. (1991). The 5-HT1A receptor: an overview of recent advances. Neurochem. Res. 16 (1): 1–10.
  • Hensler JG (2003). Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration. Life Sci. 72 (15): 1665–82.
  • Van Oekelen D, Luyten WH, Leysen JE (2003). 5-HT2A and 5-HT2C receptors and their atypical regulation properties. Life Sci. 72 (22): 2429–49.
  • Lesch KP, Gutknecht L (2005). Focus on The 5-HT1A receptor: emerging role of a gene regulatory variant in psychopathology and pharmacogenetics. Int. J. Neuropsychopharmacol. 7 (4): 381–5.
  • Kalipatnapu S, Chattopadhyay A (2006). Membrane protein solubilization: recent advances and challenges in solubilization of serotonin1A receptors. IUBMB Life 57 (7): 505–12.
  • Varrault A, Bockaert J, Waeber C (1992). Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis. Mol. Biol. Cell 3 (9): 961–9.
  • Levy FO, Gudermann T, Perez-Reyes E, et al. (1992). Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype. J. Biol. Chem. 267 (11): 7553–62.
  • Melmer G, Sherrington R, Mankoo B, et al. (1992). A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to dna loci D5S6, D5S39, and D5S76. Genomics 11 (3): 767–9.
  • Parks CL, Chang LS, Shenk T (1992). A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region. Nucleic Acids Res. 19 (25): 7155–60.
  • Gilliam TC, Freimer NB, Kaufmann CA, et al. (1990). Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia. Genomics 5 (4): 940–4.
  • Kobilka BK, Frielle T, Collins S, et al. (1987). An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 329 (6134): 75–9.
  • Fargin A, Raymond JR, Lohse MJ, et al. (1988). The genomic clone G-21, which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335 (6188): 358–60.
  • Nakhai B, Nielsen DA, Linnoila M, Goldman D (1995). Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28. Biochem. Biophys. Res. Commun. 210 (2): 530–6.
  • Aune TM, McGrath KM, Sarr T, et al. (1993). Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J. Immunol. 151 (3): 1175–83.
  • Parks CL, Shenk T (1996). The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J. Biol. Chem. 271 (8): 4417–30.
  • Stockmeier CA, Shapiro LA, Dilley GE, et al. (1998). Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J. Neurosci. 18 (18): 7394–401.
  • Kawanishi Y, Harada S, Tachikawa H, et al. (1998). Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia. Am. J. Med. Genet. 81 (5): 434–9.
  • Salim K, Fenton T, Bacha J, et al. (2002). Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation. J. Biol. Chem. 277 (18): 15482–5.




External links

  • 5-HT1A. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.


v·d·e
Cell physiology: cell signaling
Key concepts

Ligand - Cell signaling networks - Signal transduction - Apoptosis - Second messenger system (Ca2+ signaling, Lipid signaling)

Processes

Paracrine - Autocrine - Juxtacrine - Neurotransmitters - Endocrine (Neuroendocrine)

Types of proteins

Receptor (Transmembrane, Intracellular) - Transcription factor (General, Preinitiation complex, TFIID, TFIIH) - Adaptor protein

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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