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

Psychopharmacology (Berl). 1991;103(3):314-22. doi: 10.1007/BF02244284.

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)

MeSH terms

  • 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
  • Seizures / prevention & control
  • Spiro Compounds / pharmacology*

Substances

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