GABA Receptor Pharmacology

There is increasing evidence for the existence of “novel” receptors for the neurotransmitter GABA that pharmacologically fall outside the currently accepted classification of two major subtypes. The GABAA/B classification, introduced in 1981, defines GABAA receptors as being sensitive to antagonism by bicuculline and insensitive to baclofen, while GABAB receptors are insensitive to antagonism by bicuculline and are activated by baclofen. GABA receptors insensitive to both bicuculline and baclofen have been described extensively in both vertebrates and invertebrates. These “novel” GABA receptors have been given a variety of designations — GABAC, GABANANB (non-A, non-B), and ρ-receptors (cloned from retina). With the increasing evidence for similarities between these receptors, their subtype is most conveniently designated GABAC in an extension of the current GABAA/B nomenclature, though a more definitive classification of GABA receptors based on pharmacological, physiological and molecular biological considerations will emerge in due course. GABAC receptors may constitute a third major sub-class of GABA receptors distinct in structure and function from the now classical GABAA and GABAB receptors. They may represent a relatively simple form of ligand gated ion channel which are made up of homo-oligomeric subunits, in contrast to the hetero-oligomeric GABAA receptors. The more complex GABAA receptors may have evolved from the simpler GABAC receptors.