WIN 55,212-2

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WIN 55,212-2
WIN 55,212-2-2D-skeletal.svg
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
ATC code ?
PubChem CID 5311501
IUPHAR ligand 733
ChemSpider 4470978 N
ChEBI CHEBI:73295 N
ChEMBL CHEMBL188 N
Chemical data
Formula C27H26N2O3 
Mol. mass 426.52 g/mol
 N (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.[citation needed]

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]

See also[edit]

References[edit]

  1. ^ Michalski, C., et al. (2008). "Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells". In Gluud, Christian. PLoS ONE 3 (2): e1701. Bibcode:2008PLoSO...3.1701M. doi:10.1371/journal.pone.0001701. PMC 2253501. PMID 18301776.   edit
  2. ^ Compton DR, et al. Aminoalkylindole Analogs: Cannabimimetic Activity of a Class of Compounds Structurally Distinct from Δ9-Tetrahydrocannabinol. Journal of Pharmacology and Experimental Therapeutics. 1992; 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.  edit
  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.   edit
  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.  edit
  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.  edit
  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.  edit
  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) (Pt 2): 637–641. PMC 1136308. PMID 8526880.  edit
  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.   edit
  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.   edit
  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. 

External links[edit]

  • Enzo Life Sciences Win 55,212-2 Data Sheet
  • The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. 2006 Jul 18; PubMed 16849427
  • JNeurosci.org Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation
  • New Scientist: Hope for cannabis-based drug for Alzheimer's