Central GABA receptor agonists: Comparison of muscimol and baclofen

Abstract

Using a number of criteria that have helped to characterize γ-aminobutyric acid (GABA) receptor stimulation in the central nervous system, the actions of baclofen and muscimol were compared with those of diazepam and phenobarbital. The pharmacological profile of baclofen differs from that of a GABA agonist but in contrast many actions of muscimol may be a reflection of GABA receptor stimulation. These are: a selective antagonism against isoniazid seizures, a decrease in cerebellar guanosine 3′,5′ cyclic monophosphate (cyclic GMP) content and a selective anatagonism against the increase in cerebellar cyclic GMP content elicited by isoniazid. This antagonism is elicited by muscimol doses that per se fail to lower the cyclic GMP content of cerebellum. Muscimol, which is structurally related to GABA, could be a candidate for studying the pharmacology and the therapeutic potentials of GABA receptor agonists.