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A nonbenzodiazepine partial agonist, S-(+)-DN-2327, has minimal physical dependence-producing liability, but shows cross-dependence on barbital in rats.

Abstract：

:1. Physical dependence and cross-physical dependence on barbital of the benzodiazepine receptor partial agonist S-(+)-DN-2327 and the benzodiazepine receptor full agonist diazepam were compared in male Fischer 344 rats. 2. In the physical dependence study, rats were treated with S-(+)-DN-2327 (30, 100, 300 and 1000 mg/kg/day) or diazepam (30, 100 and 300 mg/kg/day) for 4 weeks by the drug admixed with food method. After stopping the treatment, the body weight and food consumption in the diazepam 100 and 300 mg/kg groups tended to decrease or decreased to values lower than those in the control group, whereas these parameters in the S-(+)-DN-2327 30, 100 and 300 mg/kg groups were comparable to the control group values. 3. In the cross-dependence study, rats were treated with increasing doses of barbital by admixing the drug with food for 4 weeks, after which the diet admixed with barbital was replaced by basal diet alone or admixed with S-(+)-DN-2327 or diazepam (target doses: 100 and 300 mg/kg/day for each compound). During the substitution period, the decreases in body weight and food consumption in both S-(+)-DN-2327 and both diazepam groups were suppressed compared with those in the basal diet group. 4. These results suggest that S-(+)-DN-2327 possesses minimal physical dependence-producing liability, but shows cross-dependence on barbital, as do benzodiazepine receptor full agonists.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Inui Y,Yamamoto M,Awasaki Y,Nishida N

doi

10.1016/s0278-5846(96)00106-6

subject

Has Abstract

pub_date

1996-10-01 00:00:00

pages

1197-211

issue

7

eissn

0278-5846

issn

1878-4216

pii

S0278584696001066

journal_volume

20

pub_type

杂志文章

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