![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 297, Issue 2, 646-656, May 2001
Department of Pharmacology and Therapeutics, University of Florida,
Gainesville, Florida (R.L.P.); and Departments of Neurosurgery and
Psychiatry and the Neuroscience Program, University of South Florida
College of Medicine, Tampa, Florida (P.R.S., D.S.)
Because mecamylamine, a nicotinic receptor antagonist, is used so often
in nicotine research and because mecamylamine may have important
therapeutic properties clinically, it is important to fully explore and
understand its pharmacology. In the present study, the efficacy and
potency of mecamylamine and its stereoisomers were evaluated as
inhibitors of human 
3
4, 32, 7, and 42 nicotinic
acetylcholine receptors (nAChRs), as well as mouse adult type muscle
nAChRs and rat N-methyl-D-aspartate (NMDA)
receptors expressed in Xenopus oocytes. The selectivity
of mecamylamine for neuronal nAChR was manifested primarily in terms of
slow recovery rates from mecamylamine-induced inhibition. Neuronal
receptors showed a prolonged inhibition after exposure to low
micromolar concentrations of mecamylamine. Muscle-type receptors showed
a transient inhibition by similar concentrations of mecamylamine, and
NMDA receptors were only transiently inhibited by higher micromolar concentrations. Mecamylamine inhibition of neuronal nAChR was noncompetitive and voltage dependent. Although there was little difference between S-(+)-mecamylamine and
R-(
)-mecamylamine in terms of 50% inhibition
concentration values for a given receptor subtype, there appeared to be
significant differences in the off-rates for the mecamylamine isomers
from the receptors. Specifically, S-(+)-mecamylamine
appeared to dissociate more slowly from 42 and 34 receptors
than did R-()-mecamylamine. In addition, it was found
that muscle-type receptors appeared to be somewhat more sensitive to
R-()-mecamylamine than to
S-(+)-mecamylamine. Together, these findings suggest
that in chronic (i.e., therapeutic) application, S-(+)-mecamylamine might be preferable to
R-()-mecamylamine in terms of equilibrium inactivation
of neuronal receptors with decreased side effects associated with
muscle-type receptors.
This article has been cited by other articles:
|
|
 |
|
  R. F. Yoshimura, D. J. Hogenkamp, W. Y. Li, M. B. Tran, J. D. Belluzzi, E. R. Whittemore, F. M. Leslie, and K. W. Gee Negative Allosteric Modulation of Nicotinic Acetylcholine Receptors Blocks Nicotine Self-Administration in Rats J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 907 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Teper, D. Whyte, E. Cahir, H. A. Lester, S. R. Grady, M. J. Marks, B. N. Cohen, C. Fonck, T. McClure-Begley, J. M. McIntosh, et al. Nicotine-Induced Dystonic Arousal Complex in a Mouse Line Harboring a Human Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy Mutation J. Neurosci., September 19, 2007; 27(38): 10128 - 10142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Abdrakhmanova, M. I. Damaj, F. I. Carroll, and B. R. Martin 2-Fluoro-3-(4-nitro-phenyl)deschloroepibatidine Is a Novel Potent Competitive Antagonist of Human Neuronal {alpha}4beta2 nAChRs Mol. Pharmacol., June 1, 2006; 69(6): 1945 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Sacco, A. Termine, A. Seyal, M. M. Dudas, J. C. Vessicchio, S. Krishnan-Sarin, P. I. Jatlow, B. E. Wexler, and T. P. George Effects of Cigarette Smoking on Spatial Working Memory and Attentional Deficits in Schizophrenia: Involvement of Nicotinic Receptor Mechanisms Arch Gen Psychiatry, June 1, 2005; 62(6): 649 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Papke, J. D. Buhr, M. M. Francis, K. I. Choi, J. S. Thinschmidt, and N. A. Horenstein The Effects of Subunit Composition on the Inhibition of Nicotinic Receptors by the Amphipathic Blocker 2,2,6,6-Tetramethylpiperidin-4-yl Heptanoate Mol. Pharmacol., June 1, 2005; 67(6): 1977 - 1990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. Salas, F. Pieri, and M. De Biasi Decreased Signs of Nicotine Withdrawal in Mice Null for the {beta}4 Nicotinic Acetylcholine Receptor Subunit J. Neurosci., November 10, 2004; 24(45): 10035 - 10039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Chernyavsky, J. Arredondo, L. M. Marubio, and S. A. Grando Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes J. Cell Sci., November 1, 2004; 117(23): 5665 - 5679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alkondon, E. F. R. Pereira, P. Yu, E. Z. Arruda, L. E. F. Almeida, P. Guidetti, W. P. Fawcett, M. T. Sapko, W. R. Randall, R. Schwarcz, et al. Targeted Deletion of the Kynurenine Aminotransferase II Gene Reveals a Critical Role of Endogenous Kynurenic Acid in the Regulation of Synaptic Transmission via {alpha}7 Nicotinic Receptors in the Hippocampus J. Neurosci., May 12, 2004; 24(19): 4635 - 4648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Liu, W. Zhu, Z.-S. Zhang, T. Yang, A. Grant, G. Oxford, and S. A. Simon Nicotine Inhibits Voltage-Dependent Sodium Channels and Sensitizes Vanilloid Receptors J Neurophysiol, April 1, 2004; 91(4): 1482 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Damaj, W. Kao, and B. R. Martin Characterization of Spontaneous and Precipitated Nicotine Withdrawal in the Mouse J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 526 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alkondon, E. F.R. Pereira, and E. X. Albuquerque NMDA and AMPA Receptors Contribute to the Nicotinic Cholinergic Excitation of CA1 Interneurons in the Rat Hippocampus J Neurophysiol, September 1, 2003; 90(3): 1613 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dunckley and R. J. Lukas Nicotine Modulates the Expression of a Diverse Set of Genes in the Neuronal SH-SY5Y Cell Line J. Biol. Chem., April 25, 2003; 278(18): 15633 - 15640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zuo, J. Z. Yeh, and T. Narahashi Dual Action of n-Butanol on Neuronal Nicotinic alpha 4beta 2 Acetylcholine Receptors J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1143 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alkondon and E. X. Albuquerque A Non-alpha 7 Nicotinic Acetylcholine Receptor Modulates Excitatory Input to Hippocampal CA1 Interneurons J Neurophysiol, March 1, 2002; 87(3): 1651 - 1654. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
