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Titolo:
EVALUATION OF THE DEPENDENCE LIABILITY OF QUINOLIZINONES ACTING AS PARTIAL AGONISTS AT THE BENZODIAZEPINE RECEPTOR
Autore:
MARTIN JR; MOREAU JL; JENCK F;
Indirizzi:
F HOFFMANN LA ROCHE LTD,PRPN,PRECLIN CNS RES,DIV PHARMA,BLDG 72-150 CH-4002 BASEL SWITZERLAND
Titolo Testata:
Drug development research
fascicolo: 3, volume: 36, anno: 1995,
pagine: 141 - 149
SICI:
0272-4391(1995)36:3<141:EOTDLO>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIGANDS; PROFILE;
Keywords:
QUINOLIZINONES; BENZODIAZEPINE RECEPTOR; PARTIAL AGONISM; PRECIPITATED WITHDRAWAL; DEPENDENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
J.R. Martin et al., "EVALUATION OF THE DEPENDENCE LIABILITY OF QUINOLIZINONES ACTING AS PARTIAL AGONISTS AT THE BENZODIAZEPINE RECEPTOR", Drug development research, 36(3), 1995, pp. 141-149

Abstract

The quinolizinones Ro 19-5663, Ro 19-5686 and Ro 41-3696 bind with high affinity to the benzodiazepine receptor (BZR) in vitro in the rat brain. These compounds exhibit anxiolytic-like effects in an operant punishment task in mice and rats and anticonvulsant effects by fully protecting against pentylenetetrazol-induced tonic seizures in mice and rats and fully protecting against audiogenic seizures in genetically susceptible mice. However, they produced at most only minimal motor impairment in the rotarod task in rodents. These compounds attenuated flunitrazepam-induced sleep in squirrel monkeys, thus antagonizing the effects of a BZR full agonist. In a precipitated withdrawal paradigm, chronic oral treatment in seizure-prone young DBA/2J mice or adult squirrel monkeys was followed by iv challenge with the BZR antagonist sarmazenil. Following the completion of a chronic treatment regiment with high doses of these quinolizinones, no signs of precipitated withdrawal were observed in mice and only weak signs of sarmazenil-induced withdrawal were observed in monkeys. In contrast, sarmazenil challenge afterchronic treatment with the BZR full agonists triazolam and alprazolamelicited marked withdrawal reactions in mice and monkeys, respectively. In sum, these quinolizinones are BZR partial agonists which offer potential anxiolytic and anticonvulsant efficacy concomitant to reducedadverse effects, including a clear reduction of dependence liability,in comparison to BZR full agonists. (C) 1995 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 06:23:53