GABAB receptor agonists and antagonists: pharmacological properties and therapeutic possibilities

Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, is widely distributed throughout the brain and spinal cord. Two major families of GABA receptors have been identified, GABAA and GABAB. While much is known about the pharmacological and molecular properties of GABAA receptors, it is only within the last few years that potent and selective antagonists have been developed for the GABAB site, and only within the past few months that this receptor has been cloned. Thus, tools are now available to define more fully the GABAB receptor in terms of its biology and the therapeutic potential of manipulating this site. Data suggest that, in addition to their established use as muscle relaxants, GABAB receptor agonists possess analgesic and antitussive properties, and may be useful for treating bladder dysfunction. While there is less clinical data on GABAB receptor antagonists, preclinical results indicate that they may be of value in treating absence epilepsy, cognitive dysfunction and, possibly, pulmonary and intestinal disorders. However, for this potential to be fully exploited, it is necessary to identify and characterise molecularly and pharmacologically distinct GABAB receptor subtypes.