A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects.
The perphenazine and fluphenazine GABA esters 3 and 4 evaluated in rat models for antipsychotic activity displayed a significant decrease of catalepsy associated with increased prolactin blood levels. Efficacy was evaluated in the d-amphetamine-induced hyperactivity model, where perphenazine abolished hyperactivity and induced sedation and catalepsy, whereas 3 reduced hyperactivity without sedation or catalepsy. Thus, 3 (BL-1020) constitutes a prototype of novel antipsychotics possessing GABAergic activity. A phase II study is in progress.
Nudelman
Abraham
A
Department of Chemistry, Bar Ilan University, Ramat Gan, Israel. adarep@post.tau.ac.il
Gil-Ad
Irit
I
Shpaisman
Nava
N
Terasenko
Igor
I
Ron
Hanna
H
Savitsky
Kinneret
K
Geffen
Yona
Y
Weizman
Abraham
A
Rephaeli
Ada
A
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D001682:Biological Availability; D002375:Catalepsy / Q000139:chemically induced; D003913:Dextroamphetamine; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D004952:Esters; D005476:Fluphenazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D010546:Perphenazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D014150:Antipsychotic Agents; D004952:Esters; D011355:Prodrugs; D005680:gamma-Aminobutyric Acid; D011388:Prolactin; D010546:Perphenazine; D005476:Fluphenazine; D003913:Dextroamphetamine