Pharmacologic profile of a new anxiolytic, DN-2327: effect of Ro15-1788 and interaction with diazepam in rodents.

Abstract

In order to characterize the pharmacologic profile of DN-2327, an isoindoline benzodiazepine (BZD) receptor ligand, its interactions with Ro15-1788 and diazepam were analyzed in rodents. The anti-conflict action of DN-2327 in two conflict tests using rats, the punished water-lick conflict (Vogel conflict) and the punished bar-pressing conflict test, was completely attenuated by treatment with Ro15-1788. The anti-convulsive (pentylenetetrazol [PTZ] induced convulsion) effect of DN-2327 was also reduced by Ro15-1788. These results suggest that the anti-conflict and anti-convulsive actions of DN-2327 may be mediated via BZD receptors. On the other hand, DN-2327 only slightly affected the motor coordination in mice and rats, as estimated by the inclined screen test and the climbing test, respectively; however, the compound attenuated the motor incoordination produced by diazepam. Furthermore, the pentobarbital potentiating effect of diazepam was reduced by pretreatment with DN-2327 in mice. In the Vogel conflict test, additive effects were observed upon the conflict test, additive effects were observed upon the concomitant administration of subeffective doses (5 mg/kg, PO) of DN-2327 and diazepam. DN-2327 at 20 mg/kg, PO, did not reduce but slightly potentiated the anti-conflict effect of the maximum effective dose of diazepam. For PTZ-induced convulsions, DN-2327, 0.5 and 20 mg/kg, PO, doses which produced partial and complete anti-convulsive effects, respectively, in rats did not reduce but increased additively the effects of diazepam. DN-2327 at 10 and 20 mg/kg, PO, doses which both produced partial anti-convulsive effects in mice, showed an additive effect with the partial effects of diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: T Wada, N Fukuda
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 103 Issue 3 Pg. 314-22 ( 1991) ISSN: 0033-3158 [Print] Germany
• PMID: 1676179 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Isoindoles
• Naphthyridines
• Receptors, GABA-A
• Spiro Compounds
• Flumazenil
• Pentobarbital
• pazinaclone
• Diazepam

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Behavior, Animal (drug effects)
• Conditioning, Operant (drug effects)
• Conflict, Psychological
• Diazepam (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Flumazenil (pharmacology)
• Isoindoles
• Male
• Mice
• Mice, Inbred ICR
• Muscle Relaxation (drug effects)
• Naphthyridines (pharmacology)
• Pentobarbital (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, GABA-A (drug effects)
• Seizures (chemically induced, prevention & control)
• Spiro Compounds (pharmacology)