Receptors in Mammalian Brain: Potential Targets for Drug Development

Young, A.B., and D. Chu : Distribution of GABA, and GABA, receptors in mammalian brain: potential targets for drug development. Drug Dev. Res. 21 :161-167, 1990. GABA is the major inhibitory neurotransmitter in mammalian brain. GABA receptors and the metabolism of GABA are significant targets for new centrally acting drugs to treat neurological and behavioral disorders. The simple neutral amino acid is likely to subserve a neurotransmitter role at 25-50% of all synapses in the central nervous system. GABA's actions are mediated by two different receptors, GABA, and GABA, receptors. GABAA receptors are ligand-gated chloride channels that are sensitive to the convulsant alkaloid bicuculline and modulated by benzodiazepines and barbiturates. GABA, receptors affect calcium and potassium conductance through GTP binding proteins and are insensitive to bicuculline and sensitive to the agonist baclofen. Both receptors are widely distributed in cerebral cortex, hippocampus, basal ganglia, thalamus, cerebellum, and brainstem.