ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
artículos
Título:
Activation-induced regulation of GABAA receptors: Is there a link with the molecular basis of benzodiazepine tolerance ?
Autor/es:
GRAVIELLE, M. C.
Revista:
PHARMACOLOGICAL RESEARCH
Editorial:
ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2016 vol. 109 p. 92 - 100
ISSN:
1043-6618
Resumen:
Benzodiazepines have been used clinically for morethan 50 years to treat disorders such as insomnia, anxiety, and epilepsy, aswell asto aid muscle relaxation and anesthesia. The therapeutic index forbenzodiazepines if very high and the toxicity is low. However,their usefulnessis limited by the development of either or both tolerance to most of theirpharmacological actions and dependence. Tolerance develops at different ratesdepending on the pharmacological action, suggesting the existence of distinctmechanisms for each behavioral parameter. Alternatively, multiple mechanismscould coexist depending on the subtype of GABAA receptor expressedand the brain region involved. Because most of the pharmacological actions ofbenzodiazepines are mediated through GABAA receptor binding,adaptive alterations in the number, structure, and/or functions of thesereceptors may play an important role in the development of tolerance. Thisreview is focused on the regulation of GABAA receptors induced bylong-term benzodiazepine exposure and its relationship with the development oftolerance. Understanding the mechanisms behind benzodiazepine tolerance iscritical for designing drugs that could maintain their efficacy during long-termtreatments.