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Science 18 October 1991:
Vol. 254. no. 5030, pp. 427 - 430
DOI: 10.1126/science.1925602
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Articles

Science, Vol 254, Issue 5030, 427-430
Copyright © 1991 by American Association for the Advancement of Science

articles

Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels

NP Franks and WR Lieb

Blackett Laboratory, Imperial College of Science, Technology & Medicine, London, United Kingdom.

Although it is generally agreed that general anesthetics ultimately act on neuronal ion channels, there is considerable controversy over whether this occurs by direct binding to protein or secondarily by nonspecific perturbation of lipids. Very pure optical isomers of the inhalational general anesthetic isoflurane exhibited clear stereoselectivity in their effects on particularly sensitive ion channels in identified molluscan central nervous system neurons. At the human median effect dose (ED50) for general anesthesia, the (+)-isomer was about twofold more effective than the (-)-isomer both in eliciting the anesthetic-activated potassium current IK(An) and in inhibiting a current mediated by neuronal nicotinic acetylcholine receptors. For inhibiting the much less sensitive transient potassium current IA, the (-)-isomer was marginally more potent than the (+)-isomer. Both isomers were equally effective at disrupting lipid bilayers.


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