Effects of ST2472, a novel antipsychotic, on prepulse inhibition.
ST2472, namely (9-piperazin-1-ylpyrrolo [2,1]-b[1,3]benzothiazepine), was previously shown to have antipsychotic activity in the conditioned avoidance response (CAR) test. In the present work we aimed at evaluating the antipsychotic potential of ST2472, administered orally at doses ranging from 0.75 to 6 mg/kg, in the prepulse inhibition (PPI) test. Apomorphine and MK801, namely (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate, were used as reference PPI disruption compounds, and were both administered subcutaneously. The typical antipsychotic haloperidol as well as the atypical antipsychotics clozapine and olanzapine was used as reference antipsychotics and administered orally. In the apomorphine-induced disruption of PPI, we found that ST2472, haloperidol, clozapine, and olanzapine were able to antagonise the effect of apomorphine. In the MK801-induced disruption of PPI, conversely, ST2472, haloperidol and clozapine failed to antagonise the effect of MK801, while the antagonistic effects of olanzapine were variable. These results confirm and further extend the antipsychotic potential of ST2472 and warrant future translational studies in humans.
Lombardo
Katia
K
Central & Peripheral Nervous System and General Pharmacology Department, R&D, Sigma-Tau Industrie Farmaceutiche Riunite SpA, Pomezia Rome, Italy. katia.lombardo@sigma-tau.it
Stasi
Maria Antonietta
MA
Borsini
Franco
F
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology*
C530482:9-piperazin-1-ylpyrrolo(2,1-b)benzothiazepine; D014150:Antipsychotic Agents; D010879:Piperazines; D011758:Pyrroles; D013841:Thiazepines; D016291:Dizocilpine Maleate; D001058:Apomorphine