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Titolo:
PRECIPITATED WITHDRAWAL IN SQUIRREL-MONKEYS AFTER REPEATED DAILY ORAL-ADMINISTRATION OF ALPRAZOLAM, DIAZEPAM, FLUNITRAZEPAM OR OXAZEPAM
Autore:
MARTIN JR; MOREAU JL; JENCK F;
Indirizzi:
F HOFFMANN LA ROCHE & CO LTD,PRECLIN RES,DIV PHARMA,GRENZACHERSTR 124CH-4002 BASEL SWITZERLAND
Titolo Testata:
Psychopharmacology
fascicolo: 3, volume: 118, anno: 1995,
pagine: 273 - 279
Fonte:
ISI
Lingua:
ENG
Soggetto:
BENZODIAZEPINE ANTAGONIST; RO 15-1788; FLUMAZENIL; DEPENDENCE; TOLERANCE; REVERSAL; RECEPTOR; BABOONS; RATS; PREVENTS;
Keywords:
PHYSICAL DEPENDENCE; PRECIPITATED WITHDRAWAL; TOLERANCE; SQUIRREL MONKEYS; ALPRAZOLAM; DIAZEPAM; FLUNITRAZEPAM; OXAZEPAM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
J.R. Martin et al., "PRECIPITATED WITHDRAWAL IN SQUIRREL-MONKEYS AFTER REPEATED DAILY ORAL-ADMINISTRATION OF ALPRAZOLAM, DIAZEPAM, FLUNITRAZEPAM OR OXAZEPAM", Psychopharmacology, 118(3), 1995, pp. 273-279

Abstract

The lowest dose of alprazolam, diazepam, flunitrazepam and oxazepam consistently to induce loss of righting reflex in squirrel monkeys or vehicle was orally administered to monkeys on 18 consecutive days: 2 mg/kg alprazolam (n = 4): 30 mg/kg diazepam (n = 4), 1 mg/kg flunitrazepam (n = 4), 280 mg/kg oxazepam (n = 5), or vehicle (n = 4). Tolerance developed rapidly for loss of righting reflex, more slowly for sleep and only minimally for muscle relaxation observed during the period immediately following daily oral administration. Injection of the specific benzodiazepine receptor antagonist flumazenil (10 mg/kg IV) 5 h after the ninth daily oral treatment produced signs of precipitated withdrawal (tremor, vomiting and/or convulsions) in one alprazolam-, four diazepam-, one flunitrazepam- and four oxazepam-treated monkeys, but notin the vehicle-treated monkeys. Physiological saline injected intravenously several days later under these same experimental conditions failed to provoke a precipitated withdrawal reaction. When flumazenil-induced precipitated withdrawal was again evaluated after the 18th daily oral treatment, withdrawal signs were observed in all alprazolam- and all diazepam-treated monkeys, as well as in three flunitrazepam- and three oxazepam-treated monkeys, but not in the vehicle-treated monkeys (convulsions were observed in one alprazolam-, two diazepam-, one flunitrazepam- and two oxazepam-treated monkeys). No signs of spontaneous withdrawal were observed in any of the monkeys during a subsequent 3-week drug-free period. Thus, repeated administration of approximately equieffective doses of these four benzodiazepines resulted in a similardevelopment of tolerance and physical dependence (indicated by the occurrence of a precipitated withdrawal reaction).

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Documento generato il 18/02/20 alle ore 05:08:12