Neurobehavioral activity in mice of N-vanillyl-arachidonyl-amide

We studied the cannabimimetic properties of N-vanillyl-arachidonoyl-amide (arvanil), a potential agonist of cannabinoid CB1 and capsaicin VR1 receptors, and an inhibitor of the facilitated transport of the endocannabinoid anandamide. Arvanil and anandamide exhibited similar affinities for the cannabinoid CB1 receptor, but arvanil was less efficacious in inducing cannabinoid CB1 receptor-mediated GTP gammaS binding. The K-i of arvanil for the vanilloid VR1 receptor was 0.28 muM. Administered i.v. to mice, arvanil was 100 times more potent than anandamide in producing hypothermia, analgesia, catalepsy and inhibiting spontaneous activity. These effects were not attenuated by the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H- pyrazole-3-carboxamide - HCl (SR141716A). Arvanil (i.t. administration) induced analgesia in the tail-flick test that was not blocked by either SR141716A or the vanilloid VR1 antagonist capsazepine. Conversely, capsaicin was less potent as an analgesic (ED50 180 ng/mouse, i.t.) and its effects attenuated by capsazepine. The analgesic effect of anandamide (i.t.) was also unaffected by SR141716A but was 750-fold less potent (ED50 20.5 mug/mouse) than capsaicin. These data indicate that the neurobehavioral effects exerted by arvanil are not due to activation of cannabinoid CB1 or vanilloid VR1 receptors. (C) 2000 Elsevier Science B.V. All rights reserved.