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, Jahrgang 64, 01.01.2013, S. 197-204.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -