GABA RECEPTORS AND GABAERGIC SYNAPSES AS TARGETS FOR DRUG DEVELOPMENT

Gamma‐amino butyric acid (GABA) is perhaps the most abundant and important rapid inhibitory neurotransmitter in the mammalian brain. Many previous studies have indicated that GABAergic synapses are involved in drug treatments or disease processes for epilepsy, anxiety, movement disorders, depression, and psychosis. In particular, the GABAA receptors, which rapidly open chloride ion channels and thereby clamp neuronal membrane potential to near the resting level, have received extensive study. GABAB receptors are functionally and structurally quite distinct, and there are subtypes of both GABAA and GABAB receptors. This brief review describes strategies that have been used to study GABA receptors and the pharmacology of drugs that act on GABAergic synapses. The eight reports that follow in this issue of Drug Development Research focus on the pharmacology of GABAA agonists and GABA uptake inhibitors as potential therapeutic agents, and they were first presented as a satellite symposium of the 1989 meeting of the Society for Neuroscience. The following reports give special reference to Cl‐966, a novel inhibitor of GABA uptake that was developed as a potential anticonvulsant based on animal studies [Taylor et al., 1990]. Unfortunately, Cl‐966 caused severe and unexpected neurological and psychological disturbances in initial clinical studies with healthy human volunteers and has been discontinued from further development [Sedman et al., 1990]. This brief review aims to give some perspective to the following papers on GABAA agonists and GABA uptake inhibitors. Copyright © 1990 Wiley‐Liss, Inc.