Benzodiazepines on trial: a research strategy for their rehabilitation.
Trends Pharmacol Sci
; 17(5): 192-200, 1996 May.
Article
em En
| MEDLINE
| ID: mdl-8669126
ABSTRACT
Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, tolerance, dependence, and the potential for drug abuse plague the clinical use of anxiolytic benzodiazepines. Benzodiazepine and non-benzodiazepine ligands that are in current clinical use act as full allosteric modulators of GABA-gated Cl- channels, and on chronic administration trigger compensatory changes in the subunit expression of GABAA receptors. In these putative abnormal receptors, full allosteric modulators have low intrinsic activity and potency, and tolerance and dependence ensue. In this review, Erminio Costa and Alessandro Guidotti discuss the development of partial allosteric modulators, such as imidazenil, which have high potency and low intrinsic activity at GABA-gated Cl- channels. Since in animals tolerant to full allosteric modulators imidazenil also fails to show cross-tolerance, it is an example of a new type of anxiolytic and anticonvulsant drug acting at GABAA receptors via benzodiazepine recognition sites.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ansiolíticos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Trends Pharmacol Sci
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos