ST2472: a new potential antipsychotic with very low liability to induce side-effects

Int J Neuropsychopharmacol. 2008 May;11(3):309-19. doi: 10.1017/S146114570700805X. Epub 2007 Oct 10.

Abstract

ST2472 was shown to bind to multiple receptors, thus resembling the affinity spectrum of atypical antipsychotics. The present study investigates its in-vivo potential antipsychotic effects. ST2472 is effective in the conditioned avoidance response (CAR) test in rats (ED50=1.5 mg/kg p.o.), a model sensitive to antipsychotics. It antagonizes amphetamine-induced hypermotility at dosages (minimal effective dose=0.7 mg/kg p.o.) that are lower than those necessary to antagonize amphetamine-induced stereotypy (minimal effective dose=30 mg/kg p.o.), in rats. This finding, together with the fact that ST2472 does not induce catalepsy in rodents at up to 100 mg/kg p.o., indicates that ST2472 has very low liability to induce extrapyramidal side-effects. ST2472 does not increase prolactinaemia after chronic treatment. In mice, ST2472 does not appear to alter blood pressure and heart rate in a significant fashion. In conclusion, ST2472 seems to be an antipsychotic with lower liability to produce side-effects than other antipsychotics, such as haloperidol, risperidone, olanzapine and clozapine, which were evaluated as reference drugs.

MeSH terms

  • Amphetamine
  • Analysis of Variance
  • Animals
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Avoidance Learning / drug effects*
  • Behavior, Animal / drug effects
  • Blood Pressure / drug effects
  • Catalepsy / drug therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Evaluation*
  • Heart Rate / drug effects
  • Hyperkinesis / chemically induced
  • Hyperkinesis / drug therapy
  • Locomotion / drug effects
  • Male
  • Motor Activity / drug effects
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Prolactin / metabolism
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / etiology
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use
  • Rats
  • Rats, Inbred F344
  • Reaction Time / drug effects
  • Statistics, Nonparametric
  • Stereotyped Behavior / drug effects
  • Thiazepines / pharmacology
  • Thiazepines / therapeutic use

Substances

  • 9-piperazin-1-ylpyrrolo(2,1-b)benzothiazepine
  • Antipsychotic Agents
  • Piperazines
  • Pyrroles
  • Thiazepines
  • Prolactin
  • Amphetamine