GABAB receptors as targets for drug action

Data obtained from studies in molecular biology indicate that there may be at least 500 forms of the receptor for the amino acid neurotransmitter gamma-aminobutyric acid (GABA), which are coupled to Cl- channels in mammalian neurones. In addition to this apparent subtyping, the receptors for GABA can be further differentiated on pharmacological grounds into GABAA and GABAB subclasses. GABAA receptors are coupled to Cl- channels, possess allosteric sites for benzodiazepines, barbiturates and neuroactive steroids and mediate fast synaptic inhibition, while GABAB receptors are coupled through G-proteins to neuronal K+ or Ca++ channels. Activation of these receptors increases K+ or decreases Ca++ conductances and mediates slow synaptic inhibition. Inhibition and potentiation of stimulated adenylyl cyclase activity can be attributed to GABAB site activation. The clinically effective muscle relaxant (-)baclofen is a selective agonist for the GABAB site but the therapeutical potential for antagonists of the receptor has yet to be examined. The present article reviews the background to GABAB receptor research and considers the future of drugs targetting the receptor.