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Vol. 293, Issue 3, 962-967, June 2000
3
4
Neuronal Nicotinic Receptors1,2
Department of Pharmacology, Georgetown University School of
Medicine, Washington, DC (S.C.H., M.B., Y.X., K.J.K.); and Algos
Pharmaceutical Corp., Neptune, New Jersey (K.E.P., F.S.C.)
Dextromethorphan (DM), a structural analog of morphine and codeine, has
been widely used as a cough suppressant for more than 40 years. DM is
not itself a potent analgesic, but it has been reported to enhance
analgesia produced by morphine and nonsteroidal anti-inflammatory
drugs. Although DM is considered to be nonaddictive, it has been
reported to reduce morphine tolerance in rats and to be useful in
helping addicted subjects to withdraw from heroin. Here we studied the
effects of DM on neuronal nicotinic receptors stably expressed in human
embryonic kidney cells. Studies were carried out to examine the effects
of DM on nicotine-stimulated whole cell currents and
nicotine-stimulated 86Rb+ efflux. We found that
both DM and its metabolite dextrorphan block nicotinic receptor
function in a noncompetitive but reversible manner, suggesting that
both drugs block the receptor channel. Consistent with blockade of the
receptor channel, neither drug competed for the nicotinic agonist
binding sites labeled by [3H]epibatidine. Although DM is
approximately 9-fold less potent than the widely used
noncompetitive nicotinic antagonist mecamylamine in blocking
nicotinic receptor function, the block by DM appears to reverse more
slowly than that by mecamylamine. These data indicate that DM is a
useful antagonist for studying nicotinic receptor function and suggest
that it might prove to be a clinically useful neuronal nicotinic
receptor antagonist, possibly helpful as an aid for helping people
addicted to nicotine to refrain from smoking, as well as in other
conditions where blockade of neuronal nicotinic receptors would be helpful.
This article has been cited by other articles:
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  M. I. Damaj, P. Flood, K. K. Ho, E. L. May, and B. R. Martin Effect of Dextrometorphan and Dextrorphan on Nicotine and Neuronal Nicotinic Receptors: In Vitro and in Vivo Selectivity J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 780 - 785. [Abstract] [Full Text] [PDF]
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 L.-H. Chow, E. Y.-K. Huang, S.-T. Ho, T.-Y. Lee, and P.-L. Tao Dextromethorphan potentiates morphine antinociception at the spinal level in rats: [Le dextromethorphane potentialise l'antinociception de la morphine au niveau rachidien chez les rats] Can J Anesth, November 1, 2004; 51(9): 905 - 910. [Abstract] [Full Text] [PDF]
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R. N. Pechnick and R. E. Poland Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 515 - 522. [Abstract] [Full Text] [PDF]
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Y. Xiao, R. D. Smith, F. S. Caruso, and K. J. Kellar Blockade of Rat alpha 3beta 4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 366 - 371. [Abstract] [Full Text] [PDF]
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 E. L. Meyer, Y. Xiao, and K. J. Kellar Agonist Regulation of Rat alpha 3beta 4 Nicotinic Acetylcholine Receptors Stably Expressed in Human Embryonic Kidney 293 Cells Mol. Pharmacol., September 1, 2001; 60(3): 568 - 576. [Abstract] [Full Text] [PDF]
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