Thiopental is a competitive inhibitor at the human alpha7 nicotinic acetylcholine receptor.
Anesth Analg
; 92(4): 930-3, 2001 Apr.
Article
en En
| MEDLINE
| ID: mdl-11273929
UNLABELLED: 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 alpha7 nAChR by using 2-electrode voltage clamp methodology. Concentration response curves for agonist were prepared in the presence of 25-250 microM 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 alpha7 nAChR. Inhibition is independent of membrane potential and the K(i(apparent)) is 13 microM of thiopental. The clinical 50% effective concentration for thiopental in humans is 25 microM. Thus, with a K(i(apparent)) of 13 microM, inhibition of the human alpha7 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 alpha7 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: The receptors 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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiopental
/
Receptores Nicotínicos
/
Anestésicos Intravenosos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Anesth Analg
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos