WIN 55,212-2 mesylate (a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) elevates the threshold for maximal electroshock-induced seizures in mice

The aim of this study was to determine the eff ect of WIN 55,212-2 mesylate (a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) on the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions were produced in mice by means of a current (sine-wave, 50 Hz, maximum 500 V, strength 4 - 14 mA, via ear-clip electrodes, 0.2-s stimulus duration, tonic hind limb extension taken as the endpoint). WIN 55,212-2 mesylate administered systemically (i.p.), 20 min before the MEST test, at doses of 5 and 10 mg/kg, did not alter the threshold for maximal electroconvulsions in mice. In contrast, WIN 55,212-2 mesylate at doses of 15 and 20 mg/kg signifi cantly elevated the threshold for maximal electroconvulsions in mice (P<0.05 and P<0.001). Linear regression analysis of WIN 55,212-2 mesylate doses and their corresponding threshold increases allowed for the determination of threshold increasing doses by 20% and 50% (TID 20 and TID 50 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID 20 and TID 50 values for WIN 55,212-2 mesylate were 6.3 and 17.2 mg/kg, respectively. Based on this preclinical study, one can ascertain that WIN 55,212- 2 mesylate dose-dependently increased the threshold for MEST-induced seizures, suggesting the anticonvulsant action of the compound in this seizure model in mice.