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 receptor s, and an inhibitor of the facilitated transport of the endocannabinoid ana ndamide. Arvanil and anandamide exhibited similar affinities for the cannab inoid CB1 receptor, but arvanil was less efficacious in inducing cannabinoi d CB1 receptor-mediated GTP gammaS binding. The K-i of arvanil for the vani lloid VR1 receptor was 0.28 muM. Administered i.v. to mice, arvanil was 100 times more potent than anandamide in producing hypothermia, analgesia, cat alepsy and inhibiting spontaneous activity. These effects were not attenuat ed by the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlor o-phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H- pyrazole-3-carboxamide - HCl (SR141716A). Arvanil (i.t. administration) induced analgesia in the tail-f lick test that was not blocked by either SR141716A or the vanilloid VR1 ant agonist capsazepine. Conversely, capsaicin was less potent as an analgesic (ED50 180 ng/mouse, i.t.) and its effects attenuated by capsazepine. The an algesic effect of anandamide (i.t.) was also unaffected by SR141716A but wa s 750-fold less potent (ED50 20.5 mug/mouse) than capsaicin. These data ind icate that the neurobehavioral effects exerted by arvanil are not due to ac tivation of cannabinoid CB1 or vanilloid VR1 receptors. (C) 2000 Elsevier S cience B.V. All rights reserved.