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.

• Authors: Y Inui, M Yamamoto, Y Awasaki, N Nishida
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 20 Issue 7 Pg. 1197-211 (Oct 1996) ISSN: 0278-5846 [Print] England
• PMID: 8938820 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• GABA-A Receptor Agonists
• Hypnotics and Sedatives
• Isoindoles
• Naphthyridines
• Spiro Compounds
• Barbital
• pazinaclone
• Diazepam

Topics

• Animals
• Anti-Anxiety Agents (administration & dosage, pharmacology)
• Area Under Curve
• Barbital (adverse effects)
• Behavior, Animal (drug effects)
• Binding, Competitive (drug effects)
• Body Weight (drug effects)
• Diazepam (adverse effects, pharmacology)
• Eating (drug effects)
• GABA-A Receptor Agonists
• Hypnotics and Sedatives (adverse effects)
• Isoindoles
• Male
• Naphthyridines (administration & dosage, pharmacology)
• Rats
• Rats, Inbred F344
• Spiro Compounds (administration & dosage, pharmacology)
• Substance Withdrawal Syndrome (psychology)
• Substance-Related Disorders (psychology)