title: A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects.
abstract: 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.
authors: Department of Chemistry, Bar Ilan University, Ramat Gan, Israel. adarep@post.tau.ac.il
authors: Abraham
authors: A
authors: Nudelman
authors: Irit
authors: I
authors: Gil-Ad
authors: Nava
authors: N
authors: Shpaisman
authors: Igor
authors: I
authors: Terasenko
authors: Hanna
authors: H
authors: Ron
authors: Kinneret
authors: K
authors: Savitsky
authors: Yona
authors: Y
authors: Geffen
authors: Abraham
authors: A
authors: Weizman
authors: Ada
authors: A
authors: Rephaeli
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D004952:Esters; D011355:Prodrugs; D005680:gamma-Aminobutyric Acid; D011388:Prolactin; D010546:Perphenazine; D005476:Fluphenazine; D003913:Dextroamphetamine