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ANESTHETIC PHARMACOLOGY

Thiopental is a Competitive Inhibitor at the Human 7 Nicotinic Acetylcholine Receptor

Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, New York

Address correspondence to Dr. Pamela Flood, Department of Anesthesiology, Columbia University, 630 West 168th St., New York, NY 10032. Address e-mail to pdf3{at}columbia.edu

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 7 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 7 nAChR. Inhibition is independent of membrane potential and the K_i(apparent) is 13 µM of thiopental. The clinical 50% effective concentration for thiopental in humans is 25 µM. Thus, with a K_i(apparent) of 13 µM, inhibition of the human 7 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 7 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.

Implications: Thereceptors for nicotine in the brain may be involved in the mechanism of general anesthetics. We have shown that a human receptor for nicotine is inhibited by the anesthetic barbiturate thiopental, at concentrations used clinically. The nicotinic receptor thus may mediate some of the actions of this drug.

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