Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
IN-VIVO HIGH INTRINSIC EFFICACY OF TRIAZOLAM - A POSITRON EMISSION TOMOGRAPHY STUDY IN NONHUMAN-PRIMATES
Autore:
BOTTLAENDER M; BROUILLET E; VARASTET M; LEBRETON C; SCHMID L; FUSEAU C; SITBON R; CROUZEL C; MAZIERE M;
Indirizzi:
SERV HOSP FREDERIC JOLIOT,CEA,DSV,CNRS,URA 1285,4 PL GEN LECLERC F-91406 ORSAY FRANCE SERV HOSP FREDERIC JOLIOT,CEA,DSV,CNRS,URA 1285 F-91406 ORSAY FRANCE UPJOHN FRANCE PARIS FRANCE
Titolo Testata:
Journal of neurochemistry
fascicolo: 3, volume: 62, anno: 1994,
pagine: 1102 - 1111
SICI:
0022-3042(1994)62:3<1102:IHIEOT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
BENZODIAZEPINE RECEPTOR OCCUPANCY; HUMAN-BRAIN; RAT-BRAIN; QUANTITATIVE-EVALUATION; GABAERGIC TRANSMISSION; PARTIAL AGONIST; BABOONS BRAIN; BINDING; INVIVO; INVITRO;
Keywords:
BENZODIAZEPINE RECEPTOR; POSITRON EMISSION TOMOGRAPHY; TRIAZOLAM; INTRINSIC EFFICACY; IN VIVO; NONHUMAN PRIMATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
M. Bottlaender et al., "IN-VIVO HIGH INTRINSIC EFFICACY OF TRIAZOLAM - A POSITRON EMISSION TOMOGRAPHY STUDY IN NONHUMAN-PRIMATES", Journal of neurochemistry, 62(3), 1994, pp. 1102-1111

Abstract

The triazolobenzodiazepine triazolam is a central-type benzodiazepinereceptor (BZR) ligand that is widely prescribed as a hypnotic agent. Triazolam produces its effects through potentiation of gamma-aminobutyric acid-mediated neurotransmission. Findings reported from in vitro binding studies showed some discrepancies concerning the pharmacological characteristics of triazolam. The present study aims to characterizein vivo the biochemical properties of triazolam, i.e., cerebral pharmacokinetics, interaction with BZR, potency, and intrinsic efficacy. Triazolam was studied in living nonhuman primates using positron emission tomography. Two different studies were carried out: (a) a direct study using [C-11]triazolam and (b) an indirect competition study using the radiolabeled BZR antagonist [C-11]flumazenil. Results showed that, in the brain in vivo, triazolam binds specifically and competitively to the BZR. Its rapid cerebral kinetics is consistent with a hypnotic profile (maximal binding after 23 min, elimination half-life of 202 min). Triazolam is very potent in displacing [C-11]flumazenil (ID50 = 28 /- 6 mu g/kg). Hill analysis of the displacement curve does not show obvious binding-site heterogeneity. Triazolam is 20 times more potent in displacing [C-11]flumazenil and 50 times more potent in inhibiting pentylenetetrazol-induced paroxysmal activity than the full benzodiazepine agonist diazepam. Interestingly, the simultaneous use of positronemission tomography and EEG recording allowed us to show that triazolampositive intrinsic efficacy is slightly higher (20%) than that of diazepam. An attractive hypothesis proposes that the severity of side effects of BZR ligands is proportional to their intrinsic efficacy. Therefore, our study shows that triazolam side effects, as for other benzodiazepines, may be related to its high intrinsic efficacy in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 17:59:20