A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects

Abraham Nudelman; Irit Gil-Ad; Nava Shpaisman; Igor Terasenko; Hanna Ron; Kinneret Savitsky; Yona Geffen; Abraham Weizman; Ada Rephaeli

doi:10.1021/jm7012453

A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects

Abraham Nudelman
, Irit Gil-Ad
, Nava Shpaisman
, Igor Terasenko
, Hanna Ron
, Kinneret Savitsky
, Yona Geffen
, Abraham Weizman
, Ada Rephaeli

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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.

Original language	English
Pages (from-to)	2858-2862
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	9
DOIs	https://doi.org/10.1021/jm7012453
State	Published - 8 May 2008

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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.",

author = "Abraham Nudelman and Irit Gil-Ad and Nava Shpaisman and Igor Terasenko and Hanna Ron and Kinneret Savitsky and Yona Geffen and Abraham Weizman and Ada Rephaeli",

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T1 - A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects

AU - Nudelman, Abraham

AU - Gil-Ad, Irit

AU - Shpaisman, Nava

AU - Terasenko, Igor

AU - Ron, Hanna

AU - Savitsky, Kinneret

AU - Geffen, Yona

AU - Weizman, Abraham

AU - Rephaeli, Ada

PY - 2008/5/8

Y1 - 2008/5/8

N2 - 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.

AB - 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.

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 9

ER -

A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects

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