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Initial Cross-Over Test of A Positive Allosteric Modulator of Alpha-7 Nicotinic Receptors to Aid Cessation in Smokers With Or Without Schizophrenia.
Perkins, Kenneth A; Roy Chengappa, K N; Karelitz, Joshua L; Boldry, Margaret C; Michael, Valerie; Herb, Taylor; Gannon, Jessica; Brar, Jaspreet; Ford, Lisa; Rassnick, Stefanie; Brunzell, Darlene H.
Afiliação
  • Perkins KA; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Roy Chengappa KN; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Karelitz JL; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Boldry MC; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Michael V; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Herb T; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Gannon J; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Brar J; Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
  • Ford L; Janssen Research and Development, Janssen Pharmaceuticals, Titusville NJ, USA.
  • Rassnick S; Janssen Research and Development, Janssen Pharmaceuticals, Titusville NJ, USA.
  • Brunzell DH; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond VA, USA.
Neuropsychopharmacology ; 43(6): 1334-1342, 2018 05.
Article em En | MEDLINE | ID: mdl-29185480
ABSTRACT
Preclinical research shows that compounds acting at α7 nicotinic receptors (nAChRs) can reduce nicotine self-administration, suggesting that a positive allosteric modulator (PAM) of α7 receptors, JNJ-39393406, may aid smoking cessation. Moreover, individuals with schizophrenia, who have very high rates of smoking, have reduced expression of α7 nAChRs and may particularly benefit from this compound. In two parallel studies using a within-subject cross-over design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2), both groups high in quit interest, attempted to initiate quitting temporarily during each of two 3-week phases. Treatments were the α7 nicotinic receptor PAM JNJ-39393406 (100 mg b.i.d.) or placebo (double-blind, counter-balanced). In each phase, all smoked ad lib with no drug on week 1 or during dose run-up on week 2, and then tried to quit every day during week 3. Abstinence (confirmed by CO <5 p.p.m.) and smoking reduction (CO <8), as well as cigarettes/day (in Study 1), were assessed daily (Monday-Friday) each quit week and compared between conditions. Secondary outcomes included abstinence symptoms (withdrawal and craving) and cognitive test responding (N-back; continuous performance task). In both studies, compared with placebo, active JNJ-39393406 did not increase the number of abstinent days nor reduce total smoking exposure. We also found no significant improvements in craving, withdrawal, or cognitive function. With this dose and study duration, our findings do not support further testing of this α7 nAChR PAM compound for possible efficacy in smoking cessation, in smokers with or without schizophrenia.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Esquizofrenia / Triazóis / Fumar / Agonistas Nicotínicos / Receptor Nicotínico de Acetilcolina alfa7 / Agentes de Cessação do Hábito de Fumar Tipo de estudo: Clinical_trials Limite: Adult / Female / Humans / Male Idioma: En Revista: Neuropsychopharmacology Assunto da revista: NEUROLOGIA / PSICOFARMACOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Esquizofrenia / Triazóis / Fumar / Agonistas Nicotínicos / Receptor Nicotínico de Acetilcolina alfa7 / Agentes de Cessação do Hábito de Fumar Tipo de estudo: Clinical_trials Limite: Adult / Female / Humans / Male Idioma: En Revista: Neuropsychopharmacology Assunto da revista: NEUROLOGIA / PSICOFARMACOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM