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Br J Pharmacol
2001 Oct 01;1344:871-9. doi: 10.1038/sj.bjp.0704315.
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Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes.
Coates KM
,
Flood P
.
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1. Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the effects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the alpha7 subunit or alpha4 and beta2 subunits expressed in Xenopus laevis oocytes. 2. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human alpha7 and alpha4beta2 nAChRs, with IC(50) values of 20 and 50 microM respectively. Inhibition of the alpha7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the alpha4beta2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more effectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both alpha7 (IC(50) value of 122 nM) and alpha4beta2 (IC(50) value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. 3. Ketamine is a noncompetitive inhibitor at both the alpha7 and alpha4beta2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the alpha7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the alpha4beta2 nAChR. 4. Since alpha7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic.
Anis,
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate.
1983, Pubmed
Anis,
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate.
1983,
Pubmed
Durieux,
Inhibition by ketamine of muscarinic acetylcholine receptor function.
1995,
Pubmed
,
Xenbase
Durieux,
Synergistic inhibition of muscarinic signaling by ketamine stereoisomers and the preservative benzethonium chloride.
1997,
Pubmed
,
Xenbase
Flood,
Alpha 4 beta 2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected.
1997,
Pubmed
,
Xenbase
Flood,
Intravenous anesthetics differentially modulate ligand-gated ion channels.
2000,
Pubmed
,
Xenbase
Friederich,
Stereospecific interaction of ketamine with nicotinic acetylcholine receptors in human sympathetic ganglion-like SH-SY5Y cells.
2000,
Pubmed
Furuya,
The effects of ketamine and propofol on neuronal nicotinic acetylcholine receptors and P2x purinoceptors in PC12 cells.
1999,
Pubmed
Grant,
Cellular and behavioral neurobiology of alcohol: receptor-mediated neuronal processes.
1995,
Pubmed
Harrison,
Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex.
1985,
Pubmed
Honey,
Ketamine and phencyclidine cause a voltage-dependent block of responses to L-aspartic acid.
1985,
Pubmed
Idvall,
Ketamine infusions: pharmacokinetics and clinical effects.
1979,
Pubmed
Little,
Study of ketamine as an obstetric anesthetic agent.
1972,
Pubmed
MacDonald,
Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones.
1991,
Pubmed
Orser,
Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors.
1997,
Pubmed
Sasaki,
Nonstereoselective inhibition of neuronal nicotinic acetylcholine receptors by ketamine isomers.
2000,
Pubmed
Scheller,
Ketamine blocks currents through mammalian nicotinic acetylcholine receptor channels by interaction with both the open and the closed state.
1996,
Pubmed
Sumikawa,
Selective actions of intravenous anesthetics on nicotinic- and muscarinic-receptor-mediated responses of the dog adrenal medulla.
1983,
Pubmed
Tallarida,
Statistical analysis of drug-drug and site-site interactions with isobolograms.
1989,
Pubmed
Violet,
Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics.
1997,
Pubmed
,
Xenbase
Wachtel,
Kinetics of nicotinic acetylcholine ion channels in the presence of intravenous anaesthetics and induction agents.
1992,
Pubmed
Yamakura,
Subunit-dependent inhibition of human neuronal nicotinic acetylcholine receptors and other ligand-gated ion channels by dissociative anesthetics ketamine and dizocilpine.
2000,
Pubmed
,
Xenbase
Zaman,
Inhibition of acetylcholine esterase and choline esterase by benzethonium chloride and avoidance of the benzethonium chloride carry-over inhibitory effect.
1997,
Pubmed
