title: Neurobehavioral activity in mice of N-vanillyl-arachidonyl-amide.
abstract: We studied the cannabimimetic properties of N-vanillyl-arachidonoyl-amide (arvanil), a potential agonist of cannabinoid CB(1) and capsaicin VR(1) receptors, and an inhibitor of the facilitated transport of the endocannabinoid anandamide. Arvanil and anandamide exhibited similar affinities for the cannabinoid CB(1) receptor, but arvanil was less efficacious in inducing cannabinoid CB(1) receptor-mediated GTPgammaS binding. The K(i) of arvanil for the vanilloid VR(1) receptor was 0.28 microM. 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 CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-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 VR(1) antagonist capsazepine. Conversely, capsaicin was less potent as an analgesic (ED(50) 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 (ED(50) 20.5 microg/mouse) than capsaicin. These data indicate that the neurobehavioral effects exerted by arvanil are not due to activation of cannabinoid CB(1) or vanilloid VR(1) receptors.
authors.affiliation: Istituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, Via Toiano 6, 80072, (NA), Arco Felice, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Marzo
authors.forename: C
authors.initials: C
authors.lastname: Breivogel
authors.forename: T
authors.initials: T
authors.lastname: Bisogno
authors.forename: D
authors.initials: D
authors.lastname: Melck
authors.forename: G
authors.initials: G
authors.lastname: Patrick
authors.forename: Q
authors.initials: Q
authors.lastname: Tao
authors.forename: A
authors.initials: A
authors.lastname: Szallasi
authors.forename: R K
authors.initials: RK
authors.lastname: Razdan
authors.forename: B R
authors.initials: BR
authors.lastname: Martin
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D016466:CHO Cells; D063385:Cannabinoid Receptor Modulators; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005989:Glycerides / Q000032:analysis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C121153:arvanil; C094503:glyceryl 2-arachidonate; D002211:Capsaicin; C078814:anandamide