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

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• 作者：Georg Winterer ; J¨¹rgen Gallinat ; J¨¹rgen Brinkmeyer ; Francesco Musso ; Johannes Kornhuber ; Norbert Thuerauf ; Dan Rujescu ; Reyna Favis ; Yu Sun ; Monique A. Franc ; Sivi Ouwerkerk-Mahadevan ; Luc Janssens ; Maarten Timmers ; Johannes R. Streffer
• 关键词：Schizophrenia ; P50 sensory gating ; CHRNA7 gene ; Positive allosteric ¦Á7 nicotinic acetylcholine receptor (nAChR) modulator ; Pharmacogenetics
• 刊名：Neuropharmacology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：64
• 期：Complete
• 页码：197-204
• 全文大小：273 K

文摘

In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric ¦Á7 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¡¯.