Reversal of mecamylamine-induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses

Ricardo Alvarez-Jimenez, Ellen P. Hart, Samantha Prins, Marieke de Kam, Joop M. A. van Gerven, Adam F. Cohen, Geert Jan Groeneveld

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aims: Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. Methods: This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study examined the effects of the nicotinic antagonist mecamylamine on a battery of cognitive and neurophysiological test with coadministration of a placebo, nicotine or galantamine in order to reverse the cognitive impairment caused by mecamylamine. Results: Thirty-three healthy subjects received a single oral dose of 30 mg of mecamylamine (or placebo) in combination with either 16 mg of oral galantamine or 21 mg of transdermal nicotine (or its double-dummy). Mecamylamine 30 mg induced significant disturbances of cognitive functions. Attention and execution of visual (fine) motor tasks was decreased, short- and long-term memory was impaired and the reaction velocity during the test was slower when compared to placebo. Mecamylamine 30 mg produced a decrease in posterior α and β power in the surface electroencephalogram, effects that were reversed by nicotine coadministration. Memory and motor coordination tests could be partially reversed by the coadministration of nicotine. Conclusions: Mecamylamine administration induced slowing of the electroencephalogram and produced decrease in performance of tests evaluating motor coordination, sustained attention and short- and long-term memory. These effects could be partially reversed by the coadministration of nicotine, and to a lesser extent by galantamine.
LanguageEnglish
Pages888-899
JournalBritish Journal of Clinical Pharmacology
Volume84
Issue number5
DOIs
Publication statusPublished - 2018

Cite this

Alvarez-Jimenez, Ricardo ; Hart, Ellen P. ; Prins, Samantha ; de Kam, Marieke ; van Gerven, Joop M. A. ; Cohen, Adam F. ; Groeneveld, Geert Jan. / Reversal of mecamylamine-induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses. In: British Journal of Clinical Pharmacology. 2018 ; Vol. 84, No. 5. pp. 888-899.
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abstract = "Aims: Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. Methods: This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study examined the effects of the nicotinic antagonist mecamylamine on a battery of cognitive and neurophysiological test with coadministration of a placebo, nicotine or galantamine in order to reverse the cognitive impairment caused by mecamylamine. Results: Thirty-three healthy subjects received a single oral dose of 30 mg of mecamylamine (or placebo) in combination with either 16 mg of oral galantamine or 21 mg of transdermal nicotine (or its double-dummy). Mecamylamine 30 mg induced significant disturbances of cognitive functions. Attention and execution of visual (fine) motor tasks was decreased, short- and long-term memory was impaired and the reaction velocity during the test was slower when compared to placebo. Mecamylamine 30 mg produced a decrease in posterior α and β power in the surface electroencephalogram, effects that were reversed by nicotine coadministration. Memory and motor coordination tests could be partially reversed by the coadministration of nicotine. Conclusions: Mecamylamine administration induced slowing of the electroencephalogram and produced decrease in performance of tests evaluating motor coordination, sustained attention and short- and long-term memory. These effects could be partially reversed by the coadministration of nicotine, and to a lesser extent by galantamine.",
author = "Ricardo Alvarez-Jimenez and Hart, {Ellen P.} and Samantha Prins and {de Kam}, Marieke and {van Gerven}, {Joop M. A.} and Cohen, {Adam F.} and Groeneveld, {Geert Jan}",
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Reversal of mecamylamine-induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses. / Alvarez-Jimenez, Ricardo; Hart, Ellen P.; Prins, Samantha; de Kam, Marieke; van Gerven, Joop M. A.; Cohen, Adam F.; Groeneveld, Geert Jan.

In: British Journal of Clinical Pharmacology, Vol. 84, No. 5, 2018, p. 888-899.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Reversal of mecamylamine-induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses

AU - Alvarez-Jimenez, Ricardo

AU - Hart, Ellen P.

AU - Prins, Samantha

AU - de Kam, Marieke

AU - van Gerven, Joop M. A.

AU - Cohen, Adam F.

AU - Groeneveld, Geert Jan

PY - 2018

Y1 - 2018

N2 - Aims: Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. Methods: This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study examined the effects of the nicotinic antagonist mecamylamine on a battery of cognitive and neurophysiological test with coadministration of a placebo, nicotine or galantamine in order to reverse the cognitive impairment caused by mecamylamine. Results: Thirty-three healthy subjects received a single oral dose of 30 mg of mecamylamine (or placebo) in combination with either 16 mg of oral galantamine or 21 mg of transdermal nicotine (or its double-dummy). Mecamylamine 30 mg induced significant disturbances of cognitive functions. Attention and execution of visual (fine) motor tasks was decreased, short- and long-term memory was impaired and the reaction velocity during the test was slower when compared to placebo. Mecamylamine 30 mg produced a decrease in posterior α and β power in the surface electroencephalogram, effects that were reversed by nicotine coadministration. Memory and motor coordination tests could be partially reversed by the coadministration of nicotine. Conclusions: Mecamylamine administration induced slowing of the electroencephalogram and produced decrease in performance of tests evaluating motor coordination, sustained attention and short- and long-term memory. These effects could be partially reversed by the coadministration of nicotine, and to a lesser extent by galantamine.

AB - Aims: Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. Methods: This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study examined the effects of the nicotinic antagonist mecamylamine on a battery of cognitive and neurophysiological test with coadministration of a placebo, nicotine or galantamine in order to reverse the cognitive impairment caused by mecamylamine. Results: Thirty-three healthy subjects received a single oral dose of 30 mg of mecamylamine (or placebo) in combination with either 16 mg of oral galantamine or 21 mg of transdermal nicotine (or its double-dummy). Mecamylamine 30 mg induced significant disturbances of cognitive functions. Attention and execution of visual (fine) motor tasks was decreased, short- and long-term memory was impaired and the reaction velocity during the test was slower when compared to placebo. Mecamylamine 30 mg produced a decrease in posterior α and β power in the surface electroencephalogram, effects that were reversed by nicotine coadministration. Memory and motor coordination tests could be partially reversed by the coadministration of nicotine. Conclusions: Mecamylamine administration induced slowing of the electroencephalogram and produced decrease in performance of tests evaluating motor coordination, sustained attention and short- and long-term memory. These effects could be partially reversed by the coadministration of nicotine, and to a lesser extent by galantamine.

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