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Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study

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Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. / Winterer, Georg; Gallinat, Jürgen; Brinkmeyer, Jürgen; Musso, Francesco; Kornhuber, Johannes; Thuerauf, Norbert; Rujescu, Dan; Favis, Reyna; Sun, Yu; Franc, Monique A; Ouwerkerk-Mahadevan, Sivi; Janssens, Luc; Timmers, Maarten; Streffer, Johannes R.

In: NEUROPHARMACOLOGY, Vol. 64, 01.01.2013, p. 197-204.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Winterer, G, Gallinat, J, Brinkmeyer, J, Musso, F, Kornhuber, J, Thuerauf, N, Rujescu, D, Favis, R, Sun, Y, Franc, MA, Ouwerkerk-Mahadevan, S, Janssens, L, Timmers, M & Streffer, JR 2013, 'Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study', NEUROPHARMACOLOGY, vol. 64, pp. 197-204. https://doi.org/10.1016/j.neuropharm.2012.06.040

APA

Winterer, G., Gallinat, J., Brinkmeyer, J., Musso, F., Kornhuber, J., Thuerauf, N., Rujescu, D., Favis, R., Sun, Y., Franc, M. A., Ouwerkerk-Mahadevan, S., Janssens, L., Timmers, M., & Streffer, J. R. (2013). Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. NEUROPHARMACOLOGY, 64, 197-204. https://doi.org/10.1016/j.neuropharm.2012.06.040

Vancouver

Winterer G, Gallinat J, Brinkmeyer J, Musso F, Kornhuber J, Thuerauf N et al. Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. NEUROPHARMACOLOGY. 2013 Jan 1;64:197-204. https://doi.org/10.1016/j.neuropharm.2012.06.040

Bibtex

@article{7ced9a24c4824634b9203bfa375d126d,
title = "Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study",
abstract = "In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric α7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia. All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics. No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG). Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects. It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed. This article is part of a Special Issue entitled 'Cognitive Enhancers'.",
keywords = "Adult, Allosteric Regulation, Antipsychotic Agents, Cognition Disorders, Cross-Over Studies, Diagnostic and Statistical Manual of Mental Disorders, Dose-Response Relationship, Drug, Double-Blind Method, Drugs, Investigational, Humans, Male, Middle Aged, Molecular Targeted Therapy, Nicotinic Agonists, Nootropic Agents, Receptors, Nicotinic, Schizophrenia, Sensory Gating, Smoking, Young Adult, alpha7 Nicotinic Acetylcholine Receptor",
author = "Georg Winterer and J{\"u}rgen Gallinat and J{\"u}rgen Brinkmeyer and Francesco Musso and Johannes Kornhuber and Norbert Thuerauf and Dan Rujescu and Reyna Favis and Yu Sun and Franc, {Monique A} and Sivi Ouwerkerk-Mahadevan and Luc Janssens and Maarten Timmers and Streffer, {Johannes R}",
note = "Copyright {\textcopyright} 2012 Elsevier Ltd. All rights reserved.",
year = "2013",
month = jan,
day = "1",
doi = "10.1016/j.neuropharm.2012.06.040",
language = "English",
volume = "64",
pages = "197--204",
journal = "NEUROPHARMACOLOGY",
issn = "0028-3908",
publisher = "Elsevier Limited",

}

RIS

TY - JOUR

T1 - Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study

AU - Winterer, Georg

AU - Gallinat, Jürgen

AU - Brinkmeyer, Jürgen

AU - Musso, Francesco

AU - Kornhuber, Johannes

AU - Thuerauf, Norbert

AU - Rujescu, Dan

AU - Favis, Reyna

AU - Sun, Yu

AU - Franc, Monique A

AU - Ouwerkerk-Mahadevan, Sivi

AU - Janssens, Luc

AU - Timmers, Maarten

AU - Streffer, Johannes R

N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric α7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia. All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics. No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG). Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects. It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

AB - In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric α7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia. All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics. No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG). Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects. It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

KW - Adult

KW - Allosteric Regulation

KW - Antipsychotic Agents

KW - Cognition Disorders

KW - Cross-Over Studies

KW - Diagnostic and Statistical Manual of Mental Disorders

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Drugs, Investigational

KW - Humans

KW - Male

KW - Middle Aged

KW - Molecular Targeted Therapy

KW - Nicotinic Agonists

KW - Nootropic Agents

KW - Receptors, Nicotinic

KW - Schizophrenia

KW - Sensory Gating

KW - Smoking

KW - Young Adult

KW - alpha7 Nicotinic Acetylcholine Receptor

U2 - 10.1016/j.neuropharm.2012.06.040

DO - 10.1016/j.neuropharm.2012.06.040

M3 - SCORING: Journal article

C2 - 22766391

VL - 64

SP - 197

EP - 204

JO - NEUROPHARMACOLOGY

JF - NEUROPHARMACOLOGY

SN - 0028-3908

ER -