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.