(+)-WIN 55,212-2 (mesylate) is a potent aminoalkylindole cannabinoid (CB) receptor agonist with Ki values of 62.3 and 3.3 nM for human recombinant CB1 and CB2 receptors, respectively. In primary cultures of rat cerebral cortex neurons, (+)-WIN 55,212-2 (mesylate) (0.01-100 nM) increases extracellular glutamate levels, displaying a bell-shaped concentration-response curve. This effect is fully counteracted by rimonabant at a concentration of 10 nM, by decreasing Ca2+ concentrations below 0.2 mM, or by the IP3 receptor antagonist xestospongin C at a concentration of 1 μM. (+)-WIN 55,212-2 (mesylate) induces release of the proinflammatory neuropeptide CGRP from trigeminal ganglion (TG) neurons in a calcium-dependent manner with an EC50 value of 26 μM.
