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Opiorphin

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Opiorphin
Opiorphin
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Infobox disclaimer and references


Opiorphin is an endogenous chemical compound first isolated from human saliva. Initial research with mice shows the compound has a painkilling effect greater than that of morphine.[1] It works by stopping the normal breakdown of enkephalins, natural pain-killing opioids in the spinal cord. It is a relatively simple molecule consisting of a five-amino acid polypeptide, Gln-Arg-Phe-Ser-Arg.[2][3][4][5][6][7][8][9]

Opiorphin pentapeptide originates from the N-terminal region of the protein PROL1 (proline-rich, lacrimal 1).[2] Opiorphin inhibits three proteases: neutral ecto-endopeptidase (MME), ecto-aminopeptidase N (ANPEP)[2] and perhaps also a dipeptidyl peptidase DPP3.[7] Such action extends the duration of enkephalin effect where the natural pain killers are released physiologically in response to specific potentially painful stimuli, in contrast with administration of narcotics, which floods the entire body and causes many undesirable adverse reactions, including addiction liability and constipation.[10][11] In addition, opiorphin may exert anti-depressive action.[12][13]

Therapeutic application of opiorphin in humans would require modifying the molecule to avoid its rapid degradation in the intestine and its poor penetration of the blood–brain barrier.[10][11]

See alsoEdit

ReferencesEdit

  1. Rougeot C, Robert F, Menz L, Bisson JF, Messaoudi M (August 2010). Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects. J. Physiol. Pharmacol. 61 (4): 483–90.
  2. 2.0 2.1 2.2 Dickinson DP, Thiesse M (April 1996). cDNA cloning of an abundant human lacrimal gland mRNA encoding a novel tear protein. Curr. Eye Res. 15 (4): 377–86.
  3. includeonly>Andy Coghlan. "Natural-born painkiller found in human saliva", New Scientist, November 13, 2006.
  4. includeonly>"Natural chemical 'beats morphine'", BBC News, November 14, 2006.
  5. includeonly>Mary Beckman. "Prolonging Painkillers", ScienceNOW, November 13, 2006.
  6. Stanović S, Boranić M, Petrovecki M, et al. (2000). Thiorphan, an inhibitor of neutral endopeptidase/enkephalinase (CD10/CALLA) enhances cell proliferation in bone marrow cultures of patients with acute leukemia in remission. Haematologia (Budap) 30 (1): 1–10.
  7. 7.0 7.1 Thanawala V, Kadam VJ, Ghosh R (October 2008). Enkephalinase inhibitors: potential agents for the management of pain. Curr Drug Targets 9 (10): 887–94.
  8. Davies KP (March 2009). The role of opiorphins (endogenous neutral endopeptidase inhibitors) in urogenital smooth muscle biology. J Sex Med 6 Suppl 3: 286–91.
  9. Tian XZ, Chen J, Xiong W, He T, Chen Q (July 2009). Effects and underlying mechanisms of human opiorphin on colonic motility and nociception in mice. Peptides 30 (7): 1348–54.
  10. 10.0 10.1 Rougeot C, Robert F, Menz L, Bisson JF, Messaoudi M (August 2010). Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects. J. Physiol. Pharmacol. 61 (4): 483–90.
  11. 11.0 11.1 Popik P, Kamysz E, Kreczko J, Wróbel M (November 2010). Human opiorphin: the lack of physiological dependence, tolerance to antinociceptive effects and abuse liability in laboratory mice. Behav. Brain Res. 213 (1): 88–93.
  12. Javelot H, Messaoudi M, Garnier S, Rougeot C (June 2010). Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways. J. Physiol. Pharmacol. 61 (3): 355–62.
  13. Yang QZ, Lu SS, Tian XZ, Yang AM, Ge WW, Chen Q (February 2011). The antidepressant-like effect of human opiorphin via opioid-dependent pathways in mice. Neurosci. Lett. 489 (2): 131–5.
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