Thiopental is a Competitive Inhibitor at the Human α7 Nicotinic Acetylcholine Receptor

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The nicotinic acetylcholine receptors (nAChRs) in the central nervous system may be a potential target for the anesthetic effects of thiopental. We evaluated the mechanism of action of thiopental on the human α7 nAChR by using 2-electrode voltage clamp methodology. Concentration response curves for agonist were prepared in the presence of 25–250 μM of thiopental. Inhibition by the S- and R-thiopental enantiomers was compared with inhibition by racemic thiopental. We found that thiopental acts as a competitive inhibitor at the human α7 nAChR. Inhibition is independent of membrane potential and the Ki(apparent) is 13 μM of thiopental. The clinical 50% effective concentration for thiopental in humans is 25 μM. Thus, with a Ki(apparent) of 13 μM, inhibition of the human α7 nAChR is within a clinically relevant range. The S- and R-enantiomers of thiopental cause inhibition indistinguishable from the inhibition caused by racemic thiopental. This discordance makes it unlikely that the α7 nAChR plays a role in loss of righting reflex induced by thiopental in mice, although nicotinic inhibition by thiopental may mediate other anesthetic effects and side effects.

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