WIN-55212-2 mesylate

WIN-55212-2 mesylate is a CB1 agonist (cannabinoid receptor agonist). WIN-55212-2 impairs contextual fear conditioning through the activation of CB1 cannabinoid receptors. Win-55212-2 attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model. WIN-55212-2 inhibits neurogenic inflammations in airway tissues.

Product information

CAS Number: 131543-23-2

Molecular Weight: 522.61

Formula: C28H30N2O6S

Synonym:

WIN-552122

WIN-55212-2

Chemical Name: [(3R)-2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone, monomethanesulfonate

Smiles: CC1=C(C(=O)C2=CC=CC3=CC=CC=C32)C2=CC=CC3OC[C@@H](CN4CCOCC4)N1C=32.CS(O)(=O)=O

InChiKey: FSGCSTPOPBJYSX-VEIFNGETSA-N

InChi: InChI=1S/C27H26N2O3.CH4O3S/c1-18-25(27(30)22-9-4-7-19-6-2-3-8-21(19)22)23-10-5-11-24-26(23)29(18)20(17-32-24)16-28-12-14-31-15-13-28;1-5(2,3)4/h2-11,20H,12-17H2,1H3;1H3,(H,2,3,4)/t20-;/m1./s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

WIN-55212-2 mesylate is more potent in CHO-CB2 cells than in CHO-CB1 cells by a factor of 6O. WIN-55212-2 mesylate has no effect on arachidonic acid release in CHO-CB2 or control CHO cells. WIN-55212-2 mesylate fails to stimulate any increase in intracellular Ca2+ up to 10 μM. In primary cultures of rat cerebral cortex neurons, WIN-55212-2 mesylate (0.01--100 nM) increases extracellular glutamate levels, displaying a bell-shaped concentration-response curve. The facilitatory effect of WIN-55212-2 mesylate (1 nM) is fully counteracted by SR141716A (10 nM), by the replacement of the normal Krebs Ringer-bicarbonate buffer with a low Ca2+ medium (0.2 mM) and by the IP(3) receptor antagonist xestospongin C (1 μM). WIN-55212-2 mesylate evokes CGRP release from TG neurons in vitro (EC50=26 μM) in a concentration- and calcium-dependent manner. WIN-55212-2 mesylate-2 neither inhibits capsaicin-evokes CGRP release nor does it inhibit forskolin-, isoproteranol- or prostaglandin E2-stimulated cAMP accumulation. WIN-55212-2 mesylate significantly inhibits (EC50=1.7 μM) 50 mm K+-evoked CGRP release by approximately 70%. WIN-55212-2 mesylate inhibition of 50 mm K+-evoked CGRP release is not reversed by antagonists of cannabinoid type 1 (CB1) receptor, but is mimicks in magnitude and potency (EC50=2.7 μM) by its cannabinoid-inactive enantiomer WIN-55212-2 mesylate-3.

In Vivo:

In the prefrontal cortex WIN-55212-2 mesylate (0.1 and 1 mg/kg i.p.) increases dialysate glutamate levels from of the awake rat, while the lower (0.01 mg/kg) and the higher (2 mg/kg) doses are ineffective. Furthermore, the WIN-55212-2 mesylate (0.1 mg/kg)- induced increase of dialysate glutamate levels is counteracted by pretreatment with the selective CB(1) receptor antagonist SR141716A (0.1 mg/kg, i.p.) and by the local perfusion with a low-calcium Ringer solution (Ca2+ 0.2 mM)[2]. WIN-55212-2 mesylate (0.5, 1, 3, 5, 10 and 15 mg/kg, i.p.) does not alter the seizure threshold at low doses, while higher doses of the drug significantly increases the threshold in a dose-dependent manner. The anticonvulsant effect of WIN-55212-2 mesylate, which is observed with doses as high as 5 mg/kg, can be observed with doses as low as 0.5 mg/kg in groups pre-treated with 20 mg/kg of pioglitazone.

References:

1. Rodríguez-Arias M, Roger-Sánchez C, Vilanova I, Revert N, Manzanedo C, Miñarro J, Aguilar MA. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait. Neural Plast. 2016;2016:6481862. doi: 10.1155/2016/6481862. Epub 2015 Dec 31. PubMed PMID: 26881125; PubMed Central PMCID: PMC4736006.
2. Shabani M, Mahnam A, Sheibani V, Janahmadi M. Alterations in the intrinsic burst activity of Purkinje neurons in offspring maternally exposed to the CB1 cannabinoid agonist WIN 55212-2. J Membr Biol. 2014 Jan;247(1):63-72. doi: 10.1007/s00232-013-9612-1. Epub 2013 Nov 12. PubMed PMID: 24218023.
3. Pinar-Sueiro S, Zorrilla Hurtado JÁ, Veiga-Crespo P, Sharma SC, Vecino E. Neuroprotective effects of topical CB1 agonist WIN 55212-2 on retinal ganglion cells after acute rise in intraocular pressure induced ischemia in rat. Exp Eye Res. 2013 May;110:55-8. doi: 10.1016/j.exer.2013.02.009. Epub 2013 Feb 20. PubMed PMID: 23454099.

Products are for research use only. Not for human use.