Discovery of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1h-1,2,4-triazole, a novel in vivo cannabinoid antagonist containing a 1,2,4-triazole motif.
A new series of 1,2,4-triazoles have been prepared and the evaluation of their cannabinoid properties have been carried out. Compound 8 showed cannabinoid silent antagonist activity in mouse vas deferens and guinea pig ileum preparations and in vivo assays (cannabinoid tetrad) in mouse. It did not have intrinsic activity in these bioassays, and therefore, it did not behave as a partial agonist or an inverse agonist.
Jagerovic
Nadine
N
Instituto de Química Médica, Consejo Superior de Investigaciones Científicas, Juan de la Cierva, 3, E-28006 Madrid, Spain. nadine@iqm.csic.es
Hernandez-Folgado
Laura
L
Alkorta
Ibon
I
Goya
Pilar
P
Navarro
Miguel
M
Serrano
Antonia
A
Rodriguez de Fonseca
Fernando
F
Dannert
M Teresa
MT
Alsasua
Angela
A
Suardiaz
Margarita
M
Pascual
David
D
Martín
Maria Isabel
MI
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002531:Cerebellum / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D014230:Triazoles