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

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.

• Authors: Maria A Stasi, Stefano Di Serio, Mario Vertechy, Antonio Schiavone, Orlando Ghirardi, Patrizia Minetti, Giuseppe Campiani, Franco Borsini, Paolo Carminati
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 11 Issue 3 Pg. 309-19 (May 2008) ISSN: 1461-1457 [Print] England
• PMID: 17925059 (Publication Type: Journal Article)

Chemical References

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

Topics

• Amphetamine
• Analysis of Variance
• Animals
• Antipsychotic Agents (pharmacology, 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, drug therapy)
• Locomotion (drug effects)
• Male
• Motor Activity (drug effects)
• Piperazines (pharmacology, therapeutic use)
• Prolactin (metabolism)
• Psychotic Disorders (drug therapy, etiology)
• Pyrroles (pharmacology, therapeutic use)
• Rats
• Rats, Inbred F344
• Reaction Time (drug effects)
• Statistics, Nonparametric
• Stereotyped Behavior (drug effects)
• Thiazepines (pharmacology, therapeutic use)