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A GABA_B Mystery: The Search for Pharmacologically Distinct GABA_B Receptors

Department of Pharmacology, Toxicology and Therapeutics Kansas University School of Medicine 3901 Rainbow Blvd., Kansas City, Kansas 66160.

The preponderance of GABAergic activity in rat brain is revealed by in situ hybridization of mRNA that encodes the GABA_BR1 receptor. The development of drugs that can usefully modulate GABA_B receptor activity hinges in part on efforts to identify and target pharmacologically distinguishable receptor subtypes.

[Image courtesy of Nature (www.nature.com) and B. Bettler. Nature 386, 239–246 (1997)]

The classification of neurotransmitter receptors into distinct pharmacological subtypes is of major importance in drug discovery. This quest is particularly important for neurotransmitter systems that are widely distributed. Because -aminobutyric acid (GABA) receptors, both GABA_A and GABA_B, are found throughout the neuroaxis, they are likely involved in all central nervous system functions. Accordingly, the therapeutic promise of GABA_B receptor manipulation depends upon the identification of subtypes than can be specifically targeted.

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