Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia.
Arch Gen Psychiatry
; 63(6): 630-8, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16754836
ABSTRACT
CONTEXT The alpha7 nicotinic acetylcholine receptor gene, CHRNA7, is associated with genetic transmission of schizophrenia and related cognitive and neurophysiological sensory gating deficits. Cognitive dysfunction is responsible for significant psychosocial disability in schizophrenia. Nicotine, a low-potency agonist at the alpha7 receptor, has some positive effects on neurophysiological and neurocognitive deficits associated with schizophrenia, which suggests that more effective receptor activation might meaningfully enhance cognition in schizophrenia. OBJECTIVES:
To determine if 3-[(2,4-dimethoxy)benzylidene]anabaseine (DMXB-A), a natural alkaloid derivative and a partial alpha7 nicotinic cholinergic agonist, significantly improves neurocognition, and to assess, by effects on P50 auditory evoked potential inhibition, whether its neurobiological actions are consistent with activation of alpha7 nicotinic receptors.DESIGN:
Randomized, double-blind crossover trial of 2 drug doses and 1 placebo.SETTING:
General clinical research center. PATIENTS Twelve persons with schizophrenia who did not smoke and were concurrently treated with antipsychotic drugs. One person was withdrawn because of a transient decrease in white blood cell count. INTERVENTION Administration of DMXB-A. MAIN OUTCOMEMEASURES:
Total scale score of the Repeatable Battery for the Assessment of Neuropsychological Status and P50 inhibitory gating.RESULTS:
Significant neurocognitive improvement was found on the Repeatable Battery for the Assessment of Neuropsychological Status total scale score, particularly for the lower DMXB-A dose compared with placebo. Effects were greater than those of nicotine in a similar study. Significant improvement in P50 inhibition also occurred. Patients generally tolerated the drug well.CONCLUSIONS:
An alpha7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia. Longer trials are needed to determine the clinical utility of this novel treatment strategy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Esquizofrenia
/
Psicologia do Esquizofrênico
/
Compostos de Benzilideno
/
Transtornos Cognitivos
/
Agonistas Nicotínicos
/
Potenciais Evocados Auditivos
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Arch Gen Psychiatry
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos