ST2472: a new potential antipsychotic with very low liability to induce side-effects.
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.
Stasi
Maria A
MA
Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, Rome, Italy. mariaantonietta.stasi@sigma-tau.it
Di Serio
Stefano
S
Vertechy
Mario
M
Schiavone
Antonio
A
Ghirardi
Orlando
O
Minetti
Patrizia
P
Campiani
Giuseppe
G
Borsini
Franco
F
Carminati
Paolo
P
D000661:Amphetamine; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002375:Catalepsy / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006339:Heart Rate / Q000187:drug effects; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011388:Prolactin / Q000378:metabolism; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D018709:Statistics, Nonparametric; D013239:Stereotyped Behavior / Q000187:drug effects; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use
C530482:9-piperazin-1-ylpyrrolo(2,1-b)benzothiazepine; D014150:Antipsychotic Agents; D010879:Piperazines; D011758:Pyrroles; D013841:Thiazepines; D011388:Prolactin; D000661:Amphetamine