PHARMACOLOGY OF GABAC RECEPTORS

The inhibitory neurotransmitter, (-aminobutyric acid (GABA), activates a variety of receptors in all areas of the central nervous system (CNS). Until recently, two receptor subtypes were known: bicuculline-sensitive GABAA and baclofen-sensitive GABAB receptors. Several lines of evidence now indicate the existence of a third class of GABA receptors. These novel GABAC receptors appear to be relatively simple ligand-gated Cl-channels with a distinctive pharmacology, in that they are not blocked by bicuculline and not modulated by barbiturates, benzodiazepines or neuroactive steroids. They are found predominantly in retina, insensitive to drugs that modulate GABAA and GABAB receptors and are activated selectively by cis-4-aminocrotonic acid (CACA). Compared with GABAA receptors, GABAC receptors are activated at lower concentrations of GABA and are less liable to desensitization. In addition, their channels open for a longer time. The pharmacology of these novel subtypes of GABA receptors may yield important therapeutic agents.