WIN 55,212-2

WIN 55,212-2
Systematic (IUPAC) name
(R)-(+)-[2,3-Dihydro-5-methyl-
3-(4-morpholinylmethyl)pyrrolo
[1,2,3-de]-1,4-benzoxazin-6-yl]-
1-napthalenylmethanone
Clinical data
Legal status
Identifiers
CAS Number 131543-23-2 YesY
PubChem CID 5311501
IUPHAR/BPS 733
ChemSpider 4470978 N
ChEBI CHEBI:73295 N
ChEMBL CHEMBL188 N
Chemical data
Formula C27H26N2O3
Molar mass 426.52 g/mol
 NYesY (what is this?)  (verify)
Pancreatic stellate cells. The cells in the lower frame are under the action of WIN 55,212-2. They are thought to assume a more "quiescent" phenotype. From Michalski et al., 2008.[1]

WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.[2][3][4]

WIN 55,212-2 is a potent cannabinoid receptor agonist[5] that has been found to be a potent analgesic[6] in a rat model of neuropathic pain.[7] It activates p42 and p44 MAP kinase via receptor-mediated signaling.[8]

At 5 µM WIN 55,212-2 inhibit ATP production in sperm in a CB1 receptor-dependent fashion.[9]

WIN 55,212-2, along with HU-210 and JWH-133, may prevent the inflammation caused by amyloid beta proteins involved in Alzheimer's disease, in addition to preventing cognitive impairment and loss of neuronal markers. This anti-inflammatory action is induced through agonist action at cannabinoid receptors, which prevents microglial activation that elicits the inflammation. Additionally, cannabinoids completely abolish neurotoxicity related to microglial activation in rat models.

WIN 55,212-2 is a full agonist at the CB1 cannabinoid receptor (Ki = 1.9 nM) and has much higher affinity than THC (Ki = 41 nM) for this receptor.[10]

WIN 55,212-2 reduces voluntary wheel running in laboratory mice, but with effects that depend on both genetic background and sex.[11]

WIN 55,212-2 is illegal in the UK[12]

See also

References

  1. ↑ Michalski, C.; et al. (2008). Gluud, Christian, ed. "Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells". PLoS ONE 3 (2): e1701. Bibcode:2008PLoSO...3.1701M. doi:10.1371/journal.pone.0001701. PMC 2253501. PMID 18301776.
  2. ↑ Compton, DR; et al. (1992). "Aminoalkylindole Analogs: Cannabimimetic Activity of a Class of Compounds Structurally Distinct from Δ9-Tetrahydrocannabinol". Journal of Pharmacology and Experimental Therapeutics 263 (3): 1118–1126.
  3. ↑ Ferraro, L.; Tomasini, M. C.; Gessa, G. L.; Bebe, B. W.; Tanganelli, S.; Antonelli, T. (2001). "The Cannabinoid Receptor Agonist WIN 55,212-2 Regulates Glutamate Transmission in Rat Cerebral Cortex: An in Vivo and in Vitro Study". Cerebral Cortex 11 (8): 728–733. doi:10.1093/cercor/11.8.728. PMID 11459762.
  4. ↑ Zhang, Q.; et al. (2002). "In vitro metabolism of R(+)-2,3-dihydro-5-methyl-3-(morpholinyl)methylpyrrolo 1,2,3-de1,4-benzoxazinyl-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist". Drug metabolism and disposition: the biological fate of chemicals 30 (10): 1077–1086. doi:10.1124/dmd.30.10.1077. PMID 12228183.
  5. ↑ Felder, C. C.; Joyce, K. E.; Briley, E. M.; Mansouri, J.; MacKie, K.; Blond, O.; Lai, Y.; Ma, A. L.; Mitchell, R. L. (1995). "Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors". Molecular Pharmacology 48 (3): 443–450. PMID 7565624.
  6. ↑ Meng, I. D.; Manning, B. H.; Martin, W. J.; Fields, H. L. (1998). "An analgesia circuit activated by cannabinoids". Nature 395 (6700): 381–383. doi:10.1038/26481. PMID 9759727.
  7. ↑ Herzberg, U.; Eliav, E.; Bennett, G. J.; Kopin, I. J. (1997). "The analgesic effects of R(+)-WIN 55,212–2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain". Neuroscience Letters 221 (2–3): 157–160. doi:10.1016/S0304-3940(96)13308-5. PMID 9121688.
  8. ↑ Bouaboula, M.; Poinot-Chazel, C.; Bourrié, B.; Canat, X.; Calandra, B.; Rinaldi-Carmona, M.; Le Fur, G.; Casellas, P. (1995). "Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1". The Biochemical Journal 312 (Pt 2): 637–641. doi:10.1042/bj3120637. PMC 1136308. PMID 8526880.
  9. ↑ Morgan, D. J.; Muller, C. H.; Murataeva, N. A.; Davis, B. J.; MacKie, K. (2012). "Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity". British Journal of Pharmacology 165 (8): 2575–2583. doi:10.1111/j.1476-5381.2011.01506.x. PMC 3423255. PMID 21615727.
  10. ↑ Kuster, J. E.; et al. (1993). "Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids". The Journal of Pharmacology and Experimental Therapeutics 264 (3): 1352–1363. PMID 8450470.
  11. ↑ Keeney BK, et al. (2012). "Sex differences in cannabinoid receptor-1 (CB1) pharmacology in mice selectively bred for high voluntary wheel-running behavior". Pharmacology, Biochemistry and Behavior 101: 528–537. doi:10.1016/j.pbb.2012.02.017.
  12. ↑ "The Misuse of Drugs Act 1971 (Amendment) Order 2013".

External links

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