3-Benzisothiazolylpiperazine Derivatives as Potential Atypical Antipsychotic Agents

A series of substituted phenethyl derivatives of 3-benzisothiazolylpiperazine incorporating potent D2 and 5-HT2A antagonist activity was investigated as an approach to a novel atypical antipsychotic agent. The in vitro profile of 8e from this series is a combination of D2 receptor affinity comparabl...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1996-01, Vol.39 (1), p.143-148
Main Authors: Howard, Harry R, Lowe, John A, Seeger, Thomas F, Seymour, Patricia A, Zorn, Stevin H, Maloney, Patrick R, Ewing, Frank E, Newman, Michael E, Schmidt, Anne W, Furman, Jerome S, Robinson, Gwendolyn L, Jackson, Elisa, Johnson, Celeste, Morrone, Jean
Format: Article
Language:English
Subjects:
Amphetamine - pharmacology
Animals
Antipsychotic Agents - chemistry
Antipsychotic Agents - pharmacology
Apomorphine - pharmacology
Avoidance Learning - drug effects
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Catalepsy - metabolism
Clozapine - pharmacology
Dopamine - metabolism
Dopamine - pharmacology
Drug Design
Humans
Medical sciences
Molecular Structure
Neuropharmacology
Pharmacology. Drug treatments
Phosphatidylinositols - antagonists & inhibitors
Phosphatidylinositols - metabolism
Piperazines - chemistry
Piperazines - pharmacology
Prazosin - antagonists & inhibitors
Prazosin - metabolism
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Receptors, Adrenergic - metabolism
Receptors, Dopamine - metabolism
Serotonin Antagonists - chemistry
Serotonin Antagonists - pharmacology
Thiazoles - chemistry
Thiazoles - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of substituted phenethyl derivatives of 3-benzisothiazolylpiperazine incorporating potent D2 and 5-HT2A antagonist activity was investigated as an approach to a novel atypical antipsychotic agent. The in vitro profile of 8e from this series is a combination of D2 receptor affinity comparable to the typical antipsychotic agent haloperidol and a 5-HT2A/D2 ratio comparable to the atypical agent clozapine. In vivo 8e possesses activity consistent with an efficacious antipsychotic agent with less tendency to induce extrapyramidal side effects in man.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm950625l