The benzodiazepine antagonist Ro 15-1788 reverses the effect of methyl-beta-carboline-3-carboxylate but not of harmaline on cerebellar cGMP and motor performance in mice.
The cerebellar cGMP level in mice was decreased in a dose-dependent manner 30 min after diazepam (ED50 = 2 mg/kg p.o.). This effect was reversed by the specific benzodiazepine antagonist Ro 15-1788. Methyl-beta-carboline-3-carboxylate (beta-CCM) and harmaline increased cGMP. Ro 15-1788 dose dependently counteracted the beta-CCM- but not the harmaline-induced increase in cGMP. In the horizontal wire test Ro 15-1788 antagonized the impairment of motor performance induced by beta-CCM, but not that induced by harmaline. These findings further support the view that harmaline in contrast to beta-carboline-3-carboxylates does not act through benzodiazepine receptors, and that Ro 15-1788 antagonizes only those convulsants and stimulants that act through specific benzodiazepine receptors.
Burkard
W P
WP
Bonetti
E P
EP
Haefely
W
W
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D002531:Cerebellum / Q000032:analysis*; D006152:Cyclic GMP / Q000032:analysis*; D005442:Flumazenil; D006246:Harmaline / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects
D000470:Alkaloids; D001570:Benzodiazepinones; D002243:Carbolines; D007211:Indoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C026072:1-methyl-beta-carboline-3-carboxylic acid; D005442:Flumazenil; D006246:Harmaline; D006152:Cyclic GMP