Arvanil, olvanil, AM 1172 and LY 2183240 (various cannabinoid CB1 receptor agonists) increase the threshold for maximal electroshock-induced seizures in mice

Abstract

Background: Recent evidence reveals therapeutic potential for cannabinoids to reduce seizure frequency, severity and duration. Animal models are useful tools to determine the potential antiseizure or antiepileptic effects of cannabinoids. The objective of this study was evaluation of the effect of arvanil, olvanil, AM 1172 and LY 2183240, the compounds interacted with endocannabinoid and/or endovanilloid systems, on convulsions in the commonly used model of convulsions in mice.

Methods: Arvanil and olvanil were injected intraperitoneally (ip) 30min and AM 1172 and LY 2183240 were administered ip 60min before the maximal electroshock seizure threshold (MEST) test. The criterion for convulsant activity was tonic hindlimb extension.

Results: Arvanil, olvanil, AM 1172 and LY 2183240 dose-dependently increased the electroconvulsive threshold in mice. The TID₂₀ (threshold increasing dose 20) values for arvanil, olvanil, AM 1172 and LY 2183240 were 0.9, 2.18, 2.48 and 3.56mgkg^-1, respectively, and the TID₅₀ (threshold increasing dose 50) values were 1.88, 6.45, 6.29 and 10.04mgkg^-1, respectively.

Conclusion: This study identified anticonvulsant effects of arvanil, olvanil, AM 1172 and LY 2183240. The order of the magnitude of the anticonvulsant effects of the examined compounds was following: arvanil>olvanil>AM 1172>LY 2183240.

Keywords: Cannabinoids; Epilepsy; Maximal electroshock seizures threshold; Seizures.