Dataset Information

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

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 ? and ? 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.

SUBMITTER: Alvarez-Jimenez R

PROVIDER: S-EPMC5903244 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

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

Alvarez-Jimenez Ricardo R Hart Ellen P EP Prins Samantha S de Kam Marieke M van Gerven Joop M A JMA Cohen Adam F AF Groeneveld Geert Jan GJ

British journal of clinical pharmacology 20180220 5

<h4>Aims</h4>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.<h4>Methods</h4>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 pla ...[more]

PMID: 29319910

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Project description:Within human physiology, systemic interactions couple physiological variables to maintain homeostasis. These interactions change according to health status and are modified by factors such as age and sex. For several physiological processes, sex-based distinctions in normal physiology are present and defined in isolation. However, new methodologies are indispensable to analyze system-wide properties and interactions with the objective of exploring differences between sexes. Here we propose a new method to construct complex inferential networks from a normalization using the clinical criteria for health of physiological variables, and the correlations between anthropometric and blood tests biomarkers of 198 healthy young participants (117 women, 81 men, from 18 to 27 years old). Physiological networks of men have less correlations, displayed higher modularity, higher small-world index, but were more vulnerable to directed attacks, whereas networks of women were more resilient. The networks of both men and women displayed sex-specific connections that are consistent with the literature. Additionally, we carried out a time-series study on heart rate variability (HRV) using Physionet's Fantasia database. Autocorrelation of HRV, variance, and Poincare's plots, as a measure of variability, are statistically significant higher in young men and statistically significant different from young women. These differences are attenuated in older men and women, that have similar HRV distributions. The network approach revealed differences in the association of variables related to glucose homeostasis, nitrogen balance, kidney function, and fat depots. The clusters of physiological variables and their roles within the network remained similar regardless of sex. Both methodologies show a higher number of associations between variables in the physiological system of women, implying redundant mechanisms of control and simultaneously showing that these systems display less variability in time than those of men, constituting a more resilient system.

Dataset Information

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

Aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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