Binding site location on GABA_A receptors determines whether mixtures of intravenous general anaesthetics interact synergistically or additively in vivo.

ABSTRACT:

Background and purpose

General anaesthetics can act on synaptic GABA_A receptors by binding to one of three classes of general anaesthetic sites. Canonical drugs that bind selectively to only one class of site are etomidate, alphaxalone, and the mephobarbital derivative, R-mTFD-MPAB. We tested the hypothesis that the general anaesthetic potencies of mixtures of such site-selective agents binding to the same or to different sites would combine additively or synergistically respectively.

Experimental approach

The potency of general anaesthetics individually or in combinations to cause loss of righting reflexes in tadpoles was determined, and the results were analysed using isobolographic methods.

Key results

The potencies of combinations of two or three site-s

SUBMITTER: Kent DE 

PROVIDER: S-EPMC6965696 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature