Effects of Anesthetic Agents on Synaptosomal GABA Disposal

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Abstract
In brain slices, halothane inhibited the metabolic breakdown of GABA, an inhibitory neurotransmitter. This inhibition leads to increased brain GABA content, presumably in the synaptic areas, and to the postulation that halothane anesthesia may arise from an enhanced synaptic inhibition due to this elevated GABA. The ability of many neurotropic agents to inhibit GABA breakdown was studied by assessing synaptosomal GABA disposal. GABA disposal by intact rat synaptosomes, which simulate miniature synapses, measures the conversion of [1-14C]GABA to 14CO2 and includes the processes of uptake, release and catabolism of GABA. The most potent inhibitor is chloroform, followed by halothane, enflurane, ether and thiopental. Pentobarbital, ethanol, paraldehyde and ketamine are weak inhibitors. Phenobarbital, morphine and phenytoin are not inhibitory at pharmacologic concentrations. Anesthetic agents show particular inhibitory action on this metabolic process in this model system where the ID10 values (i.e., concentration of a drug necessary to produce 10% inhibition of GABA disposal) correlate well with known pharmacologic potencies, ED50 values, or MAC [minimum alveolar concentration]. Anesthesia may be related to an inhibition of GABA disposal.

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