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{{BioPsy}}
 
{{BioPsy}}
'''Iprindole''' (C<sub>19</sub>H<sub>28</sub>N<sub>2</sub>), a [[5-HT2 receptor|5-HT2]] antagonist, is a [[tricyclic antidepressant]] that can be fatal when combined with [[MDMA]].
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{{Drugbox
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| verifiedrevid = 439569389
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| IUPAC_name = 3-(6,7,8,9,10,11-hexahydro- 5''H''-cycloocta[b]indol-5-yl)-''N'',''N''-dimethylpropan-1-amine
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| image = Iprindole-structure.png
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| width = 200
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| image2 = Iprindole3Dan.gif
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| width2 = 250
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<!--Clinical data-->
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| tradename =
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| pregnancy_category = ?
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| legal_status = Rx-only
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| routes_of_administration = [[Mouth|Oral]]
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<!--Pharmacokinetic data-->
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| bioavailability = ?
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| metabolism = [[Liver|Hepatic]]<ref name="pmid10379419">{{cite journal | author = Rotzinger S, Bourin M, Akimoto Y, Coutts RT, Baker GB | title = Metabolism of some "second"- and "fourth"-generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine | journal = Cellular and Molecular Neurobiology | volume = 19 | issue = 4 | pages = 427–42 | year = 1999 | month = August | pmid = 10379419 | doi = 10.1023/A:1006953923305 | url = http://www.kluweronline.com/art.pdf?issn = 0272-4340&volume = 19&page = 427}}</ref>
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| elimination_half-life = 52.5 hours<ref name="pmid7082775">{{cite journal | author = Caillé G, de Montigny C, Besner JG | title = Quantitation of iprindole in plasma by GLC | journal = Biopharmaceutics & Drug Disposition | volume = 3 | issue = 1 | pages = 11–7 | year = 1982 | pmid = 7082775 | doi = 10.1002/bdd.2510030103 | url = }}</ref>
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| excretion = [[Urine]], [[Feces]]<ref name="pmid113942">{{cite journal | author = Sisenwine SF, Tio CO, Ruelius HW | title = The disposition of [14C]iprindole in man, dog, miniature swine, rhesus monkey and rat | journal = Xenobiotica | volume = 9 | issue = 4 | pages = 237–46 | year = 1979 | month = April | pmid = 113942 | doi = 10.3109/00498257909038726 | url = http://informahealthcare.com/doi/abs/10.3109/00498257909038726}}</ref>
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<!--Identifiers-->
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| CAS_number_Ref = {{cascite|correct|??}}
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| CAS_number = 5560-72-5
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| ATC_prefix = N06
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| ATC_suffix = AA13
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| PubChem = 21722
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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| ChemSpiderID = 20417
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| UNII_Ref = {{fdacite|correct|FDA}}
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| UNII = 69U0IKR8FP
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| KEGG_Ref = {{keggcite|correct|kegg}}
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| KEGG = D04605
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| ChEMBL_Ref = {{ebicite|correct|EBI}}
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| ChEMBL = 126224
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<!--Chemical data-->
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| C = 19 | H = 28 | N = 2
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| molecular_weight = 284.439 g/mol
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| smiles = c13c(n(c2ccccc12)CCCN(C)C)CCCCCC3
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| InChI = 1/C19H28N2/c1-20(2)14-9-15-21-18-12-6-4-3-5-10-16(18)17-11-7-8-13-19(17)21/h7-8,11,13H,3-6,9-10,12,14-15H2,1-2H3
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| InChIKey = PLIGPBGDXASWPX-UHFFFAOYAT
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
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| StdInChI = 1S/C19H28N2/c1-20(2)14-9-15-21-18-12-6-4-3-5-10-16(18)17-11-7-8-13-19(17)21/h7-8,11,13H,3-6,9-10,12,14-15H2,1-2H3
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
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| StdInChIKey = PLIGPBGDXASWPX-UHFFFAOYSA-N
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}}
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'''Iprindole''' ('''Prondol''', '''Galatur''', '''Tertran'''), formerly known as '''pramindole''', is a [[tricyclic antidepressant]] (TCA) used in [[Europe]] for the treatment of [[major depressive disorder|depression]].<ref name="isbn0-7817-2468-6">{{cite book | author = Ayd, Frank J. | title = Lexicon of psychiatry, neurology, and the neurosciences | publisher = Lippincott-Williams & Wilkins | location = Philadelphia, Pa | year = 2000 | pages = | isbn = 0-7817-2468-6 | oclc = | doi = | url = http://books.google.com/?id=ea_QVG2BFy8C&lpg=PA531&dq=iprindole&pg=PA531#v=onepage&q=iprindole}}</ref><ref name="isbn0-412-54090-8">{{cite book | author = | title = Dictionary of organic compounds | publisher = Chapman & Hall | location = London | year = 1996 | pages = | isbn = 0-412-54090-8 | oclc = | doi = | url = http://books.google.com/?id=x2Su3GKCvtsC&lpg=PA3975&dq=iprindole%20prondol&pg=PA3975#v=onepage&q=}}</ref><ref name="isbn0-471-63107-8">{{cite book | author = Davison, Gerald C.; Hooley, Jill M.; Neale, John M. | title = Readings in abnormal psychology | publisher = Wiley | location = New York | year = 1989 | pages = | isbn = 0-471-63107-8 | oclc = | doi = | url = http://books.google.com/?id=jYhnhQ4X-e8C&lpg=PA186&dq=iprindole%20trimipramine&pg=PA186#v=onepage&q=iprindole}}</ref> It was introduced by [[Wyeth]] and has been used clinically since 1967.<ref name="pmid5548547">{{cite journal | author = | title = Jaundice from iprindole (Prondol) | journal = Drug and Therapeutics Bulletin | volume = 9 | issue = 3 | pages = 10–1 | year = 1971 | month = January | pmid = 5548547 | doi = | url = http://dtb.bmj.com/content/9/3/10.abstract}}</ref> Notably, iprindole was the first [[second-generation antidepressant]] to be launched.<ref name="doi:10.1002/ddr.430030302">{{cite journal | author = Horn AS, Trace RC | title = Second generation antidepressants: The pharmacological and clinical significance of selected examples | journal = Drug Development Research | volume = 3 | issue = 3 | pages = 203–211 | year = 1983 | month = January | doi = 10.1002/ddr.430030302 | url = http://www3.interscience.wiley.com/journal/109670310/abstract}}</ref>
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Iprindole is unique compared to most other TCAs in that it is a relatively weak [[reuptake inhibitor|inhibitor]] of the [[reuptake]] of [[serotonin]] and [[norepinephrine]] and instead acts predominantly as an [[receptor antagonist|antagonist]] of [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]s, hence its classification as 'second-generation'.<ref name="pmid475543">{{cite journal | author = Zis AP, Goodwin FK | title = Novel antidepressants and the biogenic amine hypothesis of depression. The case for iprindole and mianserin | journal = Archives of General Psychiatry | volume = 36 | issue = 10 | pages = 1097–1107 | year = 1979 | month = September | pmid = 475543 | doi = | url = http://archpsyc.ama-assn.org/cgi/pmidlookup?view=long&pmid=475543}}</ref><ref name="pmid166748">{{cite journal | author = Jaramillo J, Greenberg R | title = Comparative pharmacological studies on butriptyline and some related standard tricyclic antidepressants | journal = Canadian Journal of Physiology and Pharmacology | volume = 53 | issue = 1 | pages = 104–12 | year = 1975 | month = February | pmid = 166748 | doi = | url = }}</ref><ref name="pmid4451753">{{cite journal | author = Horn AS, Trace RC | title = Structure-activity relations for the inhibition of 5-hydroxytryptamine uptake by tricyclic antidepressants into synaptosomes from serotoninergic neurones in rat brain homogenates | journal = [[British Journal of Pharmacology]] | volume = 51 | issue = 3 | pages = 399–403 | year = 1974 | month = July | pmid = 4451753 | pmc = 1776771 | doi = | url = }}</ref> Additionally, [[side effect]]s of iprindole are much less prominent relative to other TCAs and it is well tolerated.<ref name="urlProgress in medicinal chemistry - Google Books">{{cite book | url = http://books.google.com/books?id=hNcBVxpSfGUC&lpg=PA25&dq=iprindole&as_brr=3&pg=PA25#v=onepage&q=&f=false | title = Progress in medicinal chemistry - Google Books | format = | work = | accessdate = }}</ref> However, iprindole's efficacy may not be as great as other TCAs, especially in regards to [[anxiety]] relief.<ref name="pmid475543"/><ref name="pmid4583430">{{cite journal | author = Rickels K, Chung HR, Csanalosi I, Sablosky L, Simon JH | title = Iprindole and imipramine in non-psychotic depressed out-patients | journal = The British Journal of Psychiatry : the Journal of Mental Science | volume = 123 | issue = 574 | pages = 329–39 | year = 1973 | month = September | pmid = 4583430 | doi = 10.1192/bjp.123.3.329| url = http://bjp.rcpsych.org/cgi/content/abstract/123/574/329}}</ref>
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== Availability ==
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Iprindole is sold under the trade name '''Prondol''' by [[Wyeth]] in the [[United Kingdom]] and [[Ireland]] for the indication of [[major depressive disorder]],<ref name="isbn0-85369-840-6">{{cite book | author = Sean C. Sweetman | title = Martindale: The Complete Drug Reference, 36th Edition | publisher = Pharmaceutical Press | location = London | year = 2009 | pages = | isbn = 0-85369-840-6 | oclc = | doi = | accessdate = }}</ref> and has also been sold as '''Galatur''' and '''Tertran''' by Wyeth as well.<ref name="urlIprindole">{{cite web | url = http://www.drugfuture.com/chemdata/Iprindole.html | title = DrugFuture.com - Iprindole}}</ref>
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It is discontinued in the whole world.
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== Chemistry ==
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On a [[chemical structure|structural]] level, iprindole differs from other TCAs in that it contains an [[indole]] nucleus, similarly to the [[heterocyclic]] [[antipsychotic]] [[oxypertine]], and has an [[Heterocyclic_compound#8-Membered_rings|eight-membered]] and [[saturation (chemistry)|saturated]] third [[functional group|ring]].<ref name="urlProgress in medicinal chemistry - Google Books"/><ref name="pmid4308422">{{cite journal | author = Baxter BL, Gluckman MI | title = Iprindole: an antidepressant which does not block REM sleep | journal = Nature | volume = 223 | issue = 5207 | pages = 750–2 | year = 1969 | month = August | pmid = 4308422 | doi = 10.1038/223750a0| url = |bibcode = 1969Natur.223..750B }}</ref>
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== Pharmacology ==
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Iprindole acts as an [[receptor antagonist|antagonist]] (or [[inverse agonist]]) at the following [[receptor (biochemistry)|receptor]]s:
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<div style="width: 600px">
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{{Col-begin}}
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{{Col-1-of-2}}
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* [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] (K<sub>d</sub> = 2,800 nM)<ref name="pmid3816971">{{cite journal | author = Wander TJ, Nelson A, Okazaki H, Richelson E | title = Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro | journal = European Journal of Pharmacology | volume = 132 | issue = 2-3 | pages = 115–21 | year = 1986 | month = December | pmid = 3816971 | doi = 10.1016/0014-2999(86)90596-0| url = }}</ref>
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* [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] (K<sub>i</sub> = 217 nM)<ref name="pmid8876023">{{cite journal | author = Pälvimäki EP, Roth BL, Majasuo H, ''et al.'' | title = Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor | journal = Psychopharmacology | volume = 126 | issue = 3 | pages = 234–40 | year = 1996 | month = August | pmid = 8876023 | doi = 10.1007/BF02246453| url = http://link.springer.de/link/service/journals/00213/bibs/6126003/61260234.htm}}</ref><ref name="pmid11907167">{{cite journal | author = Darvesh AS, Shankaran M, Gudelsky GA | title = 3,4-Methylenedioxymethamphetamine produces glycogenolysis and increases the extracellular concentration of glucose in the rat brain | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 301 | issue = 1 | pages = 138–44 | year = 2002 | month = April | pmid = 11907167 | doi = 10.1124/jpet.301.1.138| url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11907167}}</ref><ref name="pmid1182344">{{cite journal | author = Bevan P, Bradshaw CM, Szabadi E | title = Effects of iprindole on responses of single cortical and caudate neurones to monoamines and acetylcholine | journal = British Journal of Pharmacology | volume = 55 | issue = 1 | pages = 17–25 | year = 1975 | month = September | pmid = 1182344 | doi = | url = | pmc = 1666724 }}</ref><ref name="pmid6974869">{{cite journal | author = Nagayama H, Hingtgen JN, Aprison MH | title = Postsynaptic action by four antidepressive drugs in an animal model of depression | journal = Pharmacology, Biochemistry, and Behavior | volume = 15 | issue = 1 | pages = 125–30 | year = 1981 | month = July | pmid = 6974869 | doi = 10.1016/0091-3057(81)90350-6| url = }}</ref>
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* [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]] (K<sub>i</sub> = 206 nM)<ref name="pmid8876023"/><ref name="pmid11907167"/><ref name="pmid1182344"/><ref name="pmid6974869"/>
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* [[alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptor]] (K<sub>d</sub> = 2,300 nM)<ref name="pmid6086881">{{cite journal | author = Richelson E, Nelson A | title = Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 230 | issue = 1 | pages = 94–102 | year = 1984 | month = July | pmid = 6086881 | doi = | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6086881}}</ref>
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{{Col-2-of-2}}
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* [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor]] (K<sub>d</sub> = 8,600 nM)<ref name="pmid6086881"/><ref name="pmid6271559">{{cite journal | author = García-Sevilla JA, Hollingsworth PJ, Smnith CB | title = Alpha 2-adrenoreceptors on human platelets: selective labelling by [3H]clonidine and [3H]yohimbine and competitive inhibition by antidepressant drugs | journal = European Journal of Pharmacology | volume = 74 | issue = 4 | pages = 329–41 | year = 1981 | month = September | pmid = 6271559 | doi = 10.1016/0014-2999(81)90052-2| url = }}</ref>
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* [[H1 receptor|H<sub>1</sub> receptor]] (K<sub>d</sub> = 130 nM)<ref name="pmid6086881"/><ref name="pmid6146381">{{cite journal | author = Kanba S, Richelson E | title = Histamine H1 receptors in human brain labelled with [3H]doxepin | journal = Brain Research | volume = 304 | issue = 1 | pages = 1–7 | year = 1984 | month = June | pmid = 6146381 | doi = 10.1016/0006-8993(84)90856-4| url = http://linkinghub.elsevier.com/retrieve/pii/0006-8993(84)90856-4}}</ref><ref name="pmid6141518">{{cite journal | author = Hall H, Ogren SO | title = Effects of antidepressant drugs on histamine-H1 receptors in the brain | journal = Life Sciences | volume = 34 | issue = 6 | pages = 597–605 | year = 1984 | month = February | pmid = 6141518 | doi = 10.1016/0024-3205(84)90494-6| url = }}</ref><ref name="pmid6143844">{{cite journal | author = Onodera K, Ogura Y | title = Effects of histaminergic drugs on muricide induced by thiamine deficiency | journal = Japanese Journal of Pharmacology | volume = 34 | issue = 1 | pages = 15–21 | year = 1984 | month = January | pmid = 6143844 | doi = 10.1254/jjp.34.15| url = }}</ref>
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* [[H2 receptor|H<sub>2</sub> receptor]] (K<sub>d</sub> = 1,980 nM)<ref name="pmid6150708">{{cite journal | author = Tsai BS, Yellin TO | title = Differences in the interaction of histamine H2 receptor antagonists and tricyclic antidepressants with adenylate cyclase from guinea pig gastric mucosa | journal = [[Biochemical Pharmacology]] | volume = 33 | issue = 22 | pages = 3621–5 | year = 1984 | month = November | pmid = 6150708 | doi = 10.1016/0006-2952(84)90147-3| url = }}</ref>
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* [[Muscarinic acetylcholine receptor|mACh receptor]]s (K<sub>d</sub> = 2,100 nM)<ref name="pmid6297650">{{cite journal | author = El-Fakahany E, Richelson E | title = Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain | journal = British Journal of Pharmacology | volume = 78 | issue = 1 | pages = 97–102 | year = 1983 | month = January | pmid = 6297650 | pmc = 2044798 | doi = | url = }}</ref><ref name="pmid7052344">{{cite journal | author = Golds PR, Przyslo FR, Strange PG | title = The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors | journal = British Journal of Pharmacology | volume = 68 | issue = 3 | pages = 541–9 | year = 1980 | month = March | pmid = 7052344 | pmc = 2044199 | doi = | url = }}</ref><ref name="pmid62672">{{cite journal | author = Weinstock M, Cohen D | title = Tricyclic antidepressant drugs as antagonists of muscarinic receptors in sympathetic ganglia | journal = European Journal of Pharmacology | volume = 40 | issue = 2 | pages = 321–8 | year = 1976 | month = December | pmid = 62672 | doi = 10.1016/0014-2999(76)90069-8| url = }}</ref>
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{{Col-end}}
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</div>
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And as an [[reuptake inhibitor|inhibitor]] of the following [[membrane transport protein|transporter]]s:
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* [[Serotonin transporter|SERT]] (K<sub>d</sub> = 1,620 nM)<ref name="pmid9537821">{{cite journal | author = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2-3 | pages = 249–58 | year = 1997 | month = December | pmid = 9537821 | doi = 10.1016/S0014-2999(97)01393-9| url = http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)01393-9}}</ref>
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* [[Norepinephrine transporter|NET]] (K<sub>d</sub> = 1,262 nM)<ref name="pmid9537821"/>
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* [[Dopamine transporter|DAT]] (K<sub>d</sub> = 6,530 nM)<ref name="pmid9537821"/>
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It has negligible [[affinity (pharmacology)|affinity]] (>10,000 nM) for [[beta adrenergic receptor|β-adrenergic]] and [[sigma receptor]]s.<ref name="pmid8699">{{cite journal | author = Bylund DB, Snyder SH | title = Beta adrenergic receptor binding in membrane preparations from mammalian brain | journal = Molecular Pharmacology | volume = 12 | issue = 4 | pages = 568–80 | year = 1976 | month = July | pmid = 8699 | doi = | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8699}}</ref><ref name="pmid2908249">{{cite journal | author = Ganry H, Bourin M | title = Is iprindole an indirect betamimetic drug? | journal = Neuropsychobiology | volume = 20 | issue = 4 | pages = 187–93 | year = 1988 | pmid = 2908249 | doi = 10.1159/000118497| url = }}</ref><ref name="pmid8097333">{{cite journal | author = Ganry H, Bourin M | title = Has iprindole an alpha adrenergic activity? | journal = Progress in Neuro-psychopharmacology & Biological Psychiatry | volume = 17 | issue = 3 | pages = 435–51 | year = 1993 | month = May | pmid = 8097333 | doi = 10.1016/0278-5846(93)90077-6| url = }}</ref><ref name="pmid6087359">{{cite journal | author = Largent BL, Gundlach AL, Snyder SH | title = Psychotomimetic opiate receptors labeled and visualized with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 15 | pages = 4983–7 | year = 1984 | month = August | pmid = 6087359 | pmc = 391617 | doi = 10.1073/pnas.81.15.4983| url = |bibcode = 1984PNAS...81.4983L }}</ref>
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== Dosage ==
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Iprindole is used in [[dose (biochemistry)|dose]]s of 30–180&nbsp;mg daily.<ref name="isbn0-7817-2468-6"/><ref name="isbn0-521-28438-4">{{cite book | author = Wing, Lorna; Wing, J. K. | title = Psychoses of uncertain aetiology | publisher = Cambridge University Press | location = Cambridge, UK | year = 1982 | pages = | isbn = 0-521-28438-4 | oclc = | doi = | url = http://books.google.com/?id=QFI4AAAAIAAJ&lpg=PA167&pg=PA167#v=onepage&q=}}</ref>
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== Side effects ==
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Anticholinergic side effects such as [[dry mouth]] and [[constipation]] are either greatly reduced in comparison to [[imipramine]] and most other TCAs or fully lacking with iprindole.<ref name="urlProgress in medicinal chemistry - Google Books"/> However, it still has potent [[antihistamine]] effects and therefore can produce [[sedation]], though this is diminished relative to imipramine as well, perhaps due to iprindole lacking significant [[alpha blocker|alpha-blocking]] properties.<ref name="pmid4583430"/>
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== Contraindications ==
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Iprindole has been associated with [[jaundice]] and [[hepatotoxicity]] and should not be taken by [[alcoholic]]s or people with pre-existing [[liver disease]].<ref name="pmid5548547">{{cite journal | author = | title = Jaundice from iprindole (Prondol) | journal = Drug and Therapeutics Bulletin | volume = 9 | issue = 3 | pages = 10–1 | year = 1971 | month = January | pmid = 5548547 | doi = | url = }}</ref><ref name="isbn0-444-53266-8">{{cite book | author = Aronson, Jeffrey Kenneth | title = Meyler's Side Effects of Psychiatric Drugs (Meylers Side Effects) | publisher = Elsevier Science | location = Amsterdam | year = 2008 | pages = | isbn = 0-444-53266-8 | oclc = | doi = | url = http://books.google.com/?id=s0XYvuPVgaAC&lpg=PA87&dq=iprindole&pg=PA87#v=onepage&q=}}</ref><ref name="pmid4106521">{{cite journal | author = Ajdukiewicz AB, Grainger J, Scheuer PJ, Sherlock S | title = Jaundice due to iprindole | journal = Gut | volume = 12 | issue = 9 | pages = 705–8 | year = 1971 | month = September | pmid = 4106521 | pmc = 1411804 | doi = 10.1136/gut.12.9.705| url = http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=4106521}}</ref><ref name="pmid5556082">{{cite journal | author = Clift AD | title = Allergy to iprindole (Prondole) with hepatotoxicity | journal = British Medical Journal | volume = 2 | issue = 5763 | pages = 712 | year = 1971 | month = June | pmid = 5556082 | pmc = 1796275 | doi = 10.1136/bmj.2.5763.712| url = }}</ref> If such symptoms are encountered iprindole should be discontinued immediately.
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== Interactions ==
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Iprindole has been shown to be a potent inhibitor of the [[aromatic]] [[hydroxylation]] and/or [[dealkylation|''N''-dealkylation]]-mediated [[metabolism]] of many substances including, but not limited to [[octopamine]], [[amphetamine]], [[methamphetamine]], [[fenfluramine]], [[phenelzine]], [[tranylcypromine]], [[trimipramine]], and [[fluoxetine]], likely via inactivating [[cytochrome P450]] [[enzyme]]s.<ref name="pmid10379419"/><ref name="pmid3939325">{{cite journal | author = Sedlock ML, Ravitch J, Edwards DJ | title = The effects of imipramine and iprindole on the metabolism of octopamine in the rat | journal = Neuropharmacology | volume = 24 | issue = 8 | pages = 705–8 | year = 1985 | month = August | pmid = 3939325 | doi = 10.1016/0028-3908(85)90002-4| url = }}</ref><ref name="pmid2049371">{{cite journal | author = Hegadoren KM, Baker GB, Coutts RT, Dewhurst WG | title = Interactions of iprindole with fenfluramine metabolism in rat brain and liver | journal = Journal of Psychiatry & Neuroscience : JPN | volume = 16 | issue = 1 | pages = 5–11 | year = 1991 | month = March | pmid = 2049371 | pmc = 1188281 | doi = | url = }}</ref><ref name="pmid6506759">{{cite journal | author = Yamamoto T, Takano R, Egashira T, Yamanaka Y | title = Metabolism of methamphetamine, amphetamine and p-hydroxymethamphetamine by rat-liver microsomal preparations in vitro | journal = Xenobiotica | volume = 14 | issue = 11 | pages = 867–75 | year = 1984 | month = November | pmid = 6506759 | doi = 10.3109/00498258409151485 | url = http://informahealthcare.com/doi/abs/10.3109/00498258409151485}}</ref><ref name="pmid1797102">{{cite journal | author = Coutts RT, Hussain MS, Baker GB | title = Effect of iprindole on the metabolism of trimipramine in the rat | journal = Journal of Psychiatry & Neuroscience : JPN | volume = 16 | issue = 5 | pages = 272–5 | year = 1991 | month = December | pmid = 1797102 | pmc = 1188365 | doi = | url = }}</ref><ref name="pmid8204417">{{cite journal | author = Aspeslet LJ, Baker GB, Coutts RT, Torok-Both GA | title = The effects of desipramine and iprindole on levels of enantiomers of fluoxetine in rat brain and urine | journal = Chirality | volume = 6 | issue = 2 | pages = 86–90 | year = 1994 | pmid = 8204417 | doi = 10.1002/chir.530060208 | url = }}</ref> It also inhibits its own degradation.<ref name="pmid1797102"/>
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On account of these interactions, caution should be used when combining iprindole with other drugs.<ref name="pmid10379419"/> As an example, when administered with amphetamine or methamphetamine, iprindole increases their brain [[concentration]]s and prolongs their [[half-life|half-live]]s by 2- to 3-fold, strongly augmenting both their physiological effects and [[neurotoxicity]] in the process.<ref name="pmid839428">{{cite journal | author = Fuller RW, Baker JC, Molloy BB | title = Biological disposition of rigid analogs of amphetamine | journal = Journal of Pharmaceutical Sciences | volume = 66 | issue = 2 | pages = 271–2 | year = 1977 | month = February | pmid = 839428 | doi = 10.1002/jps.2600660235| url = }}</ref><ref name="pmid7384808">{{cite journal | author = Fuller RW, Hemrick-Luecke S | title = Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats | journal = Science | volume = 209 | issue = 4453 | pages = 305–7 | year = 1980 | month = July | pmid = 7384808 | doi = 10.1126/science.7384808| url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=7384808 | bibcode = 1980Sci...209..305F}}</ref><ref name="pmid6187915">{{cite journal | author = Peat MA, Warren PF, Gibb JW | title = Effects of a single dose of methamphetamine and iprindole on the serotonergic and dopaminergic system of the rat brain | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 225 | issue = 1 | pages = 126–31 | year = 1983 | month = April | pmid = 6187915 | doi = | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6187915}}</ref>
  +
  +
== Overdose ==
  +
  +
In [[overdose]], iprindole is much less [[toxic]] than most other TCAs and is considered relatively benign.<ref name="pmid3690249">{{cite journal | author = Cassidy S, Henry J | title = Fatal toxicity of antidepressant drugs in overdose | journal = British Medical Journal (Clinical Research Ed.) | volume = 295 | issue = 6605 | pages = 1021–4 | year = 1987 | month = October | pmid = 3690249 | pmc = 1248068 | doi = 10.1136/bmj.295.6605.1021| url = }}</ref> For instance, between 1974 and 1985, only two deaths associated with iprindole were recorded in the United Kingdom, whereas 278 were reported for imipramine.<ref name="pmid3690249"/> However, it should be noted that imipramine is prescribed much more often than iprindole, and for that reason this comparison is likely not entirely representative of iprindole's true capacity for fatality in overdose.
  +
  +
== See also ==
  +
* [[Tricyclic antidepressant]]
  +
  +
== References ==
  +
{{Reflist}}
  +
  +
== Further reading ==
  +
* {{cite journal | author = de Montigny C | title = Iprindole: a cornerstone in the neurobiological investigation of antidepressant treatments | journal = Modern Problems of Pharmacopsychiatry | volume = 18 | issue = | pages = 102–16 | year = 1982 | pmid = 6285182 | doi = | url = }}
  +
* {{cite journal | author = Horn AS, Trace RC | title = Second generation antidepressants: The pharmacological and clinical significance of selected examples | journal = Drug Development Research | volume = 3 | issue = 3 | pages = 203–211 | year = 1983 | month = January | doi = 10.1002/ddr.430030302 | url = http://www3.interscience.wiley.com/journal/109670310/abstract}}
   
 
{{Antidepressants}}
 
{{Antidepressants}}
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{{Anxiolytics}}
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{{Adrenergics}}
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{{Cholinergics}}
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{{Histaminergics}}
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{{Serotonergics}}
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{{Tricyclics}}
   
[[Category:Tricyclic antidepressant drugs]]
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[[Category:5-HT2 antagonists]]
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[[Category:Tricyclic antidepressants]]
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[[Category:Indoles]]
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{{enWP|Iprindole}}

Latest revision as of 08:16, September 27, 2013

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Iprindole chemical structure
Iprindole

3-(6,7,8,9,10,11-hexahydro- 5H-cycloocta[b]indol-5-yl)-N,N-dimethylpropan-1-amine
IUPAC name
CAS number
5560-72-5
ATC code

N06AA13

PubChem
21722
DrugBank
{{{DrugBank}}}
Chemical formula {{{chemical_formula}}}
Molecular weight 284.439 g/mol
Bioavailability  ?
Metabolism Hepatic[1]
Elimination half-life 52.5 hours[2]
Excretion Urine, Feces[3]
Pregnancy category  ?
Legal status Rx-only
Routes of administration Oral


Iprindole (Prondol, Galatur, Tertran), formerly known as pramindole, is a tricyclic antidepressant (TCA) used in Europe for the treatment of depression.[4][5][6] It was introduced by Wyeth and has been used clinically since 1967.[7] Notably, iprindole was the first second-generation antidepressant to be launched.[8]

Iprindole is unique compared to most other TCAs in that it is a relatively weak inhibitor of the reuptake of serotonin and norepinephrine and instead acts predominantly as an antagonist of 5-HT2 receptors, hence its classification as 'second-generation'.[9][10][11] Additionally, side effects of iprindole are much less prominent relative to other TCAs and it is well tolerated.[12] However, iprindole's efficacy may not be as great as other TCAs, especially in regards to anxiety relief.[9][13]

Availability Edit

Iprindole is sold under the trade name Prondol by Wyeth in the United Kingdom and Ireland for the indication of major depressive disorder,[14] and has also been sold as Galatur and Tertran by Wyeth as well.[15]

It is discontinued in the whole world.

Chemistry Edit

On a structural level, iprindole differs from other TCAs in that it contains an indole nucleus, similarly to the heterocyclic antipsychotic oxypertine, and has an eight-membered and saturated third ring.[12][16]

Pharmacology Edit

Iprindole acts as an antagonist (or inverse agonist) at the following receptors:

And as an inhibitor of the following transporters:

It has negligible affinity (>10,000 nM) for β-adrenergic and sigma receptors.[32][33][34][35]

Dosage Edit

Iprindole is used in doses of 30–180 mg daily.[4][36]

Side effects Edit

Anticholinergic side effects such as dry mouth and constipation are either greatly reduced in comparison to imipramine and most other TCAs or fully lacking with iprindole.[12] However, it still has potent antihistamine effects and therefore can produce sedation, though this is diminished relative to imipramine as well, perhaps due to iprindole lacking significant alpha-blocking properties.[13]

Contraindications Edit

Iprindole has been associated with jaundice and hepatotoxicity and should not be taken by alcoholics or people with pre-existing liver disease.[7][37][38][39] If such symptoms are encountered iprindole should be discontinued immediately.

Interactions Edit

Iprindole has been shown to be a potent inhibitor of the aromatic hydroxylation and/or N-dealkylation-mediated metabolism of many substances including, but not limited to octopamine, amphetamine, methamphetamine, fenfluramine, phenelzine, tranylcypromine, trimipramine, and fluoxetine, likely via inactivating cytochrome P450 enzymes.[1][40][41][42][43][44] It also inhibits its own degradation.[43]

On account of these interactions, caution should be used when combining iprindole with other drugs.[1] As an example, when administered with amphetamine or methamphetamine, iprindole increases their brain concentrations and prolongs their half-lives by 2- to 3-fold, strongly augmenting both their physiological effects and neurotoxicity in the process.[45][46][47]

Overdose Edit

In overdose, iprindole is much less toxic than most other TCAs and is considered relatively benign.[48] For instance, between 1974 and 1985, only two deaths associated with iprindole were recorded in the United Kingdom, whereas 278 were reported for imipramine.[48] However, it should be noted that imipramine is prescribed much more often than iprindole, and for that reason this comparison is likely not entirely representative of iprindole's true capacity for fatality in overdose.

See also Edit

References Edit

  1. 1.0 1.1 1.2 Rotzinger S, Bourin M, Akimoto Y, Coutts RT, Baker GB (August 1999). = 0272-4340&volume = 19&page = 427 Metabolism of some "second"- and "fourth"-generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine. Cellular and Molecular Neurobiology 19 (4): 427–42.
  2. Caillé G, de Montigny C, Besner JG (1982). Quantitation of iprindole in plasma by GLC. Biopharmaceutics & Drug Disposition 3 (1): 11–7.
  3. Sisenwine SF, Tio CO, Ruelius HW (April 1979). The disposition of [14Ciprindole in man, dog, miniature swine, rhesus monkey and rat]. Xenobiotica 9 (4): 237–46.
  4. 4.0 4.1 Ayd, Frank J. (2000). Lexicon of psychiatry, neurology, and the neurosciences, Philadelphia, Pa: Lippincott-Williams & Wilkins.
  5. (1996) Dictionary of organic compounds, London: Chapman & Hall.
  6. Davison, Gerald C.; Hooley, Jill M.; Neale, John M. (1989). Readings in abnormal psychology, New York: Wiley.
  7. 7.0 7.1 (January 1971)Jaundice from iprindole (Prondol). Drug and Therapeutics Bulletin 9 (3): 10–1.
  8. Horn AS, Trace RC (January 1983). Second generation antidepressants: The pharmacological and clinical significance of selected examples. Drug Development Research 3 (3): 203–211.
  9. 9.0 9.1 Zis AP, Goodwin FK (September 1979). Novel antidepressants and the biogenic amine hypothesis of depression. The case for iprindole and mianserin. Archives of General Psychiatry 36 (10): 1097–1107.
  10. Jaramillo J, Greenberg R (February 1975). Comparative pharmacological studies on butriptyline and some related standard tricyclic antidepressants. Canadian Journal of Physiology and Pharmacology 53 (1): 104–12.
  11. Horn AS, Trace RC (July 1974). Structure-activity relations for the inhibition of 5-hydroxytryptamine uptake by tricyclic antidepressants into synaptosomes from serotoninergic neurones in rat brain homogenates. British Journal of Pharmacology 51 (3): 399–403.
  12. 12.0 12.1 12.2 Progress in medicinal chemistry - Google Books.
  13. 13.0 13.1 Rickels K, Chung HR, Csanalosi I, Sablosky L, Simon JH (September 1973). Iprindole and imipramine in non-psychotic depressed out-patients. The British Journal of Psychiatry : the Journal of Mental Science 123 (574): 329–39.
  14. Sean C. Sweetman (2009). Martindale: The Complete Drug Reference, 36th Edition, London: Pharmaceutical Press.
  15. DrugFuture.com - Iprindole.
  16. Baxter BL, Gluckman MI (August 1969). Iprindole: an antidepressant which does not block REM sleep. Nature 223 (5207): 750–2.
  17. Wander TJ, Nelson A, Okazaki H, Richelson E (December 1986). Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro. European Journal of Pharmacology 132 (2-3): 115–21.
  18. 18.0 18.1 Pälvimäki EP, Roth BL, Majasuo H, et al. (August 1996). Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology 126 (3): 234–40.
  19. 19.0 19.1 Darvesh AS, Shankaran M, Gudelsky GA (April 2002). 3,4-Methylenedioxymethamphetamine produces glycogenolysis and increases the extracellular concentration of glucose in the rat brain. The Journal of Pharmacology and Experimental Therapeutics 301 (1): 138–44.
  20. 20.0 20.1 Bevan P, Bradshaw CM, Szabadi E (September 1975). Effects of iprindole on responses of single cortical and caudate neurones to monoamines and acetylcholine. British Journal of Pharmacology 55 (1): 17–25.
  21. 21.0 21.1 Nagayama H, Hingtgen JN, Aprison MH (July 1981). Postsynaptic action by four antidepressive drugs in an animal model of depression. Pharmacology, Biochemistry, and Behavior 15 (1): 125–30.
  22. 22.0 22.1 22.2 Richelson E, Nelson A (July 1984). Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. The Journal of Pharmacology and Experimental Therapeutics 230 (1): 94–102.
  23. García-Sevilla JA, Hollingsworth PJ, Smnith CB (September 1981). Alpha 2-adrenoreceptors on human platelets: selective labelling by [3H]clonidine and [3H]yohimbine and competitive inhibition by antidepressant drugs. European Journal of Pharmacology 74 (4): 329–41.
  24. Kanba S, Richelson E (June 1984). Histamine H1 receptors in human brain labelled with [3Hdoxepin]. Brain Research 304 (1): 1–7.
  25. Hall H, Ogren SO (February 1984). Effects of antidepressant drugs on histamine-H1 receptors in the brain. Life Sciences 34 (6): 597–605.
  26. Onodera K, Ogura Y (January 1984). Effects of histaminergic drugs on muricide induced by thiamine deficiency. Japanese Journal of Pharmacology 34 (1): 15–21.
  27. Tsai BS, Yellin TO (November 1984). Differences in the interaction of histamine H2 receptor antagonists and tricyclic antidepressants with adenylate cyclase from guinea pig gastric mucosa. Biochemical Pharmacology 33 (22): 3621–5.
  28. El-Fakahany E, Richelson E (January 1983). Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. British Journal of Pharmacology 78 (1): 97–102.
  29. Golds PR, Przyslo FR, Strange PG (March 1980). The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. British Journal of Pharmacology 68 (3): 541–9.
  30. Weinstock M, Cohen D (December 1976). Tricyclic antidepressant drugs as antagonists of muscarinic receptors in sympathetic ganglia. European Journal of Pharmacology 40 (2): 321–8.
  31. 31.0 31.1 31.2 Tatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). Pharmacological profile of antidepressants and related compounds at human monoamine transporters. European Journal of Pharmacology 340 (2-3): 249–58.
  32. Bylund DB, Snyder SH (July 1976). Beta adrenergic receptor binding in membrane preparations from mammalian brain. Molecular Pharmacology 12 (4): 568–80.
  33. Ganry H, Bourin M (1988). Is iprindole an indirect betamimetic drug?. Neuropsychobiology 20 (4): 187–93.
  34. Ganry H, Bourin M (May 1993). Has iprindole an alpha adrenergic activity?. Progress in Neuro-psychopharmacology & Biological Psychiatry 17 (3): 435–51.
  35. Largent BL, Gundlach AL, Snyder SH (August 1984). Psychotomimetic opiate receptors labeled and visualized with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. Proceedings of the National Academy of Sciences of the United States of America 81 (15): 4983–7.
  36. Wing, Lorna; Wing, J. K. (1982). Psychoses of uncertain aetiology, Cambridge, UK: Cambridge University Press.
  37. Aronson, Jeffrey Kenneth (2008). Meyler's Side Effects of Psychiatric Drugs (Meylers Side Effects), Amsterdam: Elsevier Science.
  38. Ajdukiewicz AB, Grainger J, Scheuer PJ, Sherlock S (September 1971). Jaundice due to iprindole. Gut 12 (9): 705–8.
  39. Clift AD (June 1971). Allergy to iprindole (Prondole) with hepatotoxicity. British Medical Journal 2 (5763): 712.
  40. Sedlock ML, Ravitch J, Edwards DJ (August 1985). The effects of imipramine and iprindole on the metabolism of octopamine in the rat. Neuropharmacology 24 (8): 705–8.
  41. Hegadoren KM, Baker GB, Coutts RT, Dewhurst WG (March 1991). Interactions of iprindole with fenfluramine metabolism in rat brain and liver. Journal of Psychiatry & Neuroscience : JPN 16 (1): 5–11.
  42. Yamamoto T, Takano R, Egashira T, Yamanaka Y (November 1984). Metabolism of methamphetamine, amphetamine and p-hydroxymethamphetamine by rat-liver microsomal preparations in vitro. Xenobiotica 14 (11): 867–75.
  43. 43.0 43.1 Coutts RT, Hussain MS, Baker GB (December 1991). Effect of iprindole on the metabolism of trimipramine in the rat. Journal of Psychiatry & Neuroscience : JPN 16 (5): 272–5.
  44. Aspeslet LJ, Baker GB, Coutts RT, Torok-Both GA (1994). The effects of desipramine and iprindole on levels of enantiomers of fluoxetine in rat brain and urine. Chirality 6 (2): 86–90.
  45. Fuller RW, Baker JC, Molloy BB (February 1977). Biological disposition of rigid analogs of amphetamine. Journal of Pharmaceutical Sciences 66 (2): 271–2.
  46. Fuller RW, Hemrick-Luecke S (July 1980). Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats. Science 209 (4453): 305–7.
  47. Peat MA, Warren PF, Gibb JW (April 1983). Effects of a single dose of methamphetamine and iprindole on the serotonergic and dopaminergic system of the rat brain. The Journal of Pharmacology and Experimental Therapeutics 225 (1): 126–31.
  48. 48.0 48.1 Cassidy S, Henry J (October 1987). Fatal toxicity of antidepressant drugs in overdose. British Medical Journal (Clinical Research Ed.) 295 (6605): 1021–4.

Further reading Edit


Antidepressants (ATC N06A) edit
Monoamine oxidase inhibitors (MAOI) Harmaline, Iproclozide, Iproniazid, Isocarboxazid, Nialamide, Phenelzine, Selegiline, Toloxatone, Tranylcypromine
Reversible inhibitor of monoamine oxidase A (RIMA) Brofaromine, Moclobemide
Dopamine reuptake inhibitor (DARI) Amineptine, Phenmetrazine, Vanoxerine, Modafinil
Norepinephrine-dopamine reuptake inhibitors Bupropion
Norepinephrine reuptake inhibitor (NRI) or (NARI) Atomoxetine, Maprotiline, Reboxetine, Viloxazine
Serotonin-norepinephrine reuptake inhibitor (SNRI) Duloxetine, Milnacipran, Venlafaxine
Selective serotonin reuptake inhibitor (SSRI) Alaproclate, Etoperidone, Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Zimelidine
Selective serotonin reuptake enhancer (SSRE) Tianeptine
Tricyclic antidepressants (TCA) Amitriptyline, Amoxapine, Butriptyline, Clomipramine, Desipramine, Dibenzepin, Dothiepin, Doxepin, Imipramine, Iprindole, Lofepramine, Melitracen, Nortriptyline, Opipramol, Protriptyline, Trimipramine
Tetracyclic antidepressants Maprotiline, Mianserin, Nefazodone, Trazodone
Noradrenergic and specific serotonergic antidepressant (NaSSA) Mirtazapine

Template:Tricyclics

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