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Titolo:
EFFECT OF THE CHRONIC DOSE OF DIAZEPAM ON THE INTENSITY AND CHARACTERISTICS OF THE PRECIPITATED ABSTINENCE SYNDROME IN THE DOG
Autore:
SLOAN JW; MARTIN WR; WALA E;
Indirizzi:
UNIV KENTUCKY,COLL MED,DEPT ANESTHESIOL,ROOM 244,RES FACIL 3 LEXINGTON KY 40536
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 265, anno: 1993,
pagine: 1152 - 1162
SICI:
0022-3565(1993)265:3<1152:EOTCDO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
BENZODIAZEPINE RECEPTOR ANTAGONIST; TERM THERAPEUTIC USE; PHYSICAL-DEPENDENCE; LONG-TERM; BINDING-SITES; RO 15-1788; N-DESMETHYLDIAZEPAM; WITHDRAWAL REACTION; CONTROLLED TRIAL; ABUSE LIABILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
89
Recensione:
Indirizzi per estratti:
Citazione:
J.W. Sloan et al., "EFFECT OF THE CHRONIC DOSE OF DIAZEPAM ON THE INTENSITY AND CHARACTERISTICS OF THE PRECIPITATED ABSTINENCE SYNDROME IN THE DOG", The Journal of pharmacology and experimental therapeutics, 265(3), 1993, pp. 1152-1162

Abstract

The ability of different chronic doses of diazepam to produce dependence was studied in groups of six dogs who received diazepam p.o. (0.05625, 0.225, 0.5625, 4.5, 9 or 36 mg/kg/day) every 8 hr. After 5 to 6 weeks of stabilization, the intensity of precipitated abstinence was measured by benzodiazepine-precipitated abstinence scores (BPAS) after the p.o. administration of graded doses of the benzodiazepine antagonist, flumazenil (0.66, 2, 6, 18, 36 and 72 mg/kg or a placebo). A modified Latin square design was used. Dogs receiving the two lowest stabilization doses of diazepam showed only liminal signs of precipitated abstinence even with 72 mg/kg of flumazenil. The intensity of the precipitated abstinence syndrome increased with the stabilization dose of diazepam. There was also a dose-related increase in BPAS for increasing doses of flumazenil for all doses of diazepam except the 9-mg/kg/day dose. Not only were quantitative differences observed in precipitated abstinence signs for different levels of diazepam dependence, but the pattern of abstinence signs differed also. Dogs dependent on high doses of diazepam were more sensitive to flumazenil than those dependent on lower doses. Furthermore, seizure activity was seem only in dogs dependent on 9 and 36 mg/kg/day of diazepam. BPAS increased linearly with plasma and brain total and free levels of the sum of diazepam and its metabolites (oxazepam and nordiazepam), but not with free plasma and brain levels of diazepam.

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Documento generato il 06/04/20 alle ore 08:17:01