WIN 55212-2 (mesylate) is a potent aminoalkylindole cannabinoid (CB) receptor agonist with a K_i of 3.3 and 62.3 nM for human recombinant CB₁ and CB₂ receptors, respectively.¹ 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.² This effect at a concentration of 1 nM was fully counteracted by SR141716A (10 nM), by decreasing Ca2+ concentrations below 0.2 mM, and by the IP₃ receptor antagonist xestospongin C at 1 µM. WIN 55212-2 (mesylate) induces release of the proinflammatory neuropeptide CGRP from trigeminal ganglion (TG) neurons in a calcium-dependent manner with an EC₅₀ of 26 µM.³ In addition, WIN 55212-2 (mesylate)-evoked CGRP release is not stereospecific, as the CB receptor-inactive enantiomer WIN 55212-3 also stimulates CGRP exocytosis.

1 Felder, C.C., Joyce, K.E., Briley, E.M., et al. Comparison of the pharmacology and signal transduction of the human cannabinoid CB₁ and CB₂ receptors. Mol Pharmacol 48 443-450 (1995).

2 Ferraro, L., Tomasini, C., Gessa, G.L., et al. The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in rat cerebral cortex: An in vivo and in vitro study. Cereb Cortex 11 728-733 (2001).

3 Price, T.J., Patwardhan, A., Akopian, A.N., et al. Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons. Br J Pharmacol 142 257-266 (2004).

Felder, C.C., Joyce, K.E., Briley, E.M., et al. Comparison of the pharmacology and signal transduction of the human cannabinoid CB₁ and CB₂ receptors. Mol Pharmacol 48 443-450 (1995).

Price, T.J., Patwardhan, A., Akopian, A.N., et al. Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons. Br J Pharmacol 142 257-266 (2004).

Ferraro, L., Tomasini, C., Gessa, G.L., et al. The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in rat cerebral cortex: An in vivo and in vitro study. Cereb Cortex 11 728-733 (2001).

WIN 55212-2 (mesylate) is available in the following screening library:

• Bio-active Lipid I Screening Library (96-Well)