Chemistry:Opiorphin
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| IUPAC name
(2S,5S,8S,11S,14S)-14,17-diamino-8-benzyl-2,11-bis(3-guanidinopropyl)-5-(hydroxymethyl)-4,7,10,13,17-pentaoxo-3,6,9,12-tetraazaheptadecan-1-oic acid
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| Other names
Gln-Arg-Phe-Ser-Arg; L-Glutaminyl-L-arginyl-L-phenylalanyl-L-seryl-L-arginine
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3D model (JSmol)
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PubChem CID
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| Properties | |
| C29H48N12O8 | |
| Molar mass | 692.779 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
 verify (what is   ?)
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| Infobox 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.[2] It works by stopping the normal breakup 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 (QRFSR).[3][4][5][6][7][8][9][10]
Opiorphin pentapeptide originates from the N-terminal region of the protein PROL1 (proline-rich, lacrimal 1).[3] Opiorphin inhibits three proteases: neutral ecto-endopeptidase (MME), ecto-aminopeptidase N (ANPEP)[3] and perhaps also a dipeptidyl peptidase DPP3.[8] 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.[11][12] In addition, opiorphin may exert anti-depressive[13][14] and antipanic action.[15]
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.[11][12] This modification is done in the body by transformation of N-terminal glutamine into pyroglutamate. This form preserves the analgesic properties of opiorphin but with increased pharmaceutical stability.[16]
See also
References
- ↑ Opiorphin at Sigma-Aldrich
- ↑ "Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects". J. Physiol. Pharmacol. 61 (4): 483–490. August 2010. PMID 20814077.
- ↑ 3.0 3.1 3.2 "cDNA cloning of an abundant human lacrimal gland mRNA encoding a novel tear protein". Curr. Eye Res. 15 (4): 377–386. April 1996. doi:10.3109/02713689608995828. PMID 8670737.
- ↑ Andy Coghlan (November 13, 2006). "Natural-born painkiller found in human saliva". New Scientist. https://www.newscientist.com/article.ns?id=dn10514.
- ↑ "Natural chemical 'beats morphine'". BBC News. November 14, 2006. http://news.bbc.co.uk/2/hi/health/6142842.stm.
- ↑ Mary Beckman (November 13, 2006). "Prolonging Painkillers". ScienceNOW. http://sciencenow.sciencemag.org/cgi/content/short/2006/1113/3.
- ↑ "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. 2000. doi:10.1163/15685590051129814. PMID 10841318.
- ↑ 8.0 8.1 "Enkephalinase inhibitors: potential agents for the management of pain". Curr Drug Targets 9 (10): 887–894. October 2008. doi:10.2174/138945008785909356. PMID 18855623.
- ↑ Davies KP (March 2009). "The role of opiorphins (endogenous neutral endopeptidase inhibitors) in urogenital smooth muscle biology". J Sex Med 6 (Suppl 3): 286–291. doi:10.1111/j.1743-6109.2008.01186.x. PMID 19267851.
- ↑ "Effects and underlying mechanisms of human opiorphin on colonic motility and nociception in mice". Peptides 30 (7): 1348–1354. July 2009. doi:10.1016/j.peptides.2009.04.002. PMID 19442408.
- ↑ 11.0 11.1 "Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects". J. Physiol. Pharmacol. 61 (4): 483–490. August 2010. PMID 20814077. http://www.jpp.krakow.pl/journal/archive/08_10/pdf/483_08_10_article.pdf.
- ↑ 12.0 12.1 "Human opiorphin: the lack of physiological dependence, tolerance to antinociceptive effects and abuse liability in laboratory mice". Behav. Brain Res. 213 (1): 88–93. November 2010. doi:10.1016/j.bbr.2010.04.045. PMID 20438769.
- ↑ "Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways". J. Physiol. Pharmacol. 61 (3): 355–362. June 2010. PMID 20610867. http://www.jpp.krakow.pl/journal/archive/06_10/pdf/355_06_10_article.pdf.
- ↑ "The antidepressant-like effect of human opiorphin via opioid-dependent pathways in mice". Neurosci. Lett. 489 (2): 131–135. February 2011. doi:10.1016/j.neulet.2010.12.002. PMID 21145938.
- ↑ Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Bonfim, Antonio Joaquim; Kitayama, Mariana; Graeff, Frederico Guilherme; Zangrossi Jr., Hélio; Audi, Elisabeth Aparecida (2016-02-01). "Opiorphin causes a panicolytic-like effect in rat panic models mediated by μ-opioid receptors in the dorsal periaqueductal gray". Neuropharmacology 101: 264–270. doi:10.1016/j.neuropharm.2015.09.008. PMID 26363194.
- ↑ Sitbon, Philippe; Van Elstraete, Alain; Hamdi, Leila; Juarez-Perez, Victor; Mazoit, Jean-Xavier; Benhamou, Dan; Rougeot, Catherine (2016-11-01). "STR-324, a Stable Analog of Opiorphin, Causes Analgesia in Postoperative Pain by Activating Endogenous Opioid Receptor-dependent Pathways". Anesthesiology 125 (5): 1017–1029. doi:10.1097/ALN.0000000000001320. ISSN 1528-1175. PMID 27571257.
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