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'.
authors: Cologne Center for Genomics, University of Cologne, Cologne, Germany. georg.winterer@uni-koeln.de
authors: Georg
authors: G
authors: Winterer
authors: Jürgen
authors: J
authors: Gallinat
authors: Jürgen
authors: J
authors: Brinkmeyer
authors: Francesco
authors: F
authors: Musso
authors: Johannes
authors: J
authors: Kornhuber
authors: Norbert
authors: N
authors: Thuerauf
authors: Dan
authors: D
authors: Rujescu
authors: Reyna
authors: R
authors: Favis
authors: Yu
authors: Y
authors: Sun
authors: Monique A
authors: MA
authors: Franc
authors: Sivi
authors: S
authors: Ouwerkerk-Mahadevan
authors: Luc
authors: L
authors: Janssens
authors: Maarten
authors: M
authors: Timmers
authors: Johannes R
authors: JR
authors: Streffer
mesh_terms: D000328:Adult; D000494:Allosteric Regulation; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D018592:Cross-Over Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects*; D012907:Smoking; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D014150:Antipsychotic Agents; C579167:Chrna7 protein, human; D015507:Drugs, Investigational; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor