Abstract
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.
MeSH terms
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Amphetamine / pharmacology
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Animals
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Antipsychotic Agents / chemistry
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Antipsychotic Agents / pharmacology*
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Apomorphine / pharmacology
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Avoidance Learning / drug effects
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Brain / drug effects
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Brain / metabolism
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Catalepsy / metabolism
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Clozapine / pharmacology
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Dopamine / metabolism
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Dopamine / pharmacology
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Drug Design
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Humans
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Molecular Structure
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Phosphatidylinositols / antagonists & inhibitors
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Phosphatidylinositols / metabolism
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Piperazines / chemistry
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Piperazines / pharmacology*
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Prazosin / antagonists & inhibitors
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Prazosin / metabolism
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Rats
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Receptors, Adrenergic / metabolism
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Receptors, Dopamine / metabolism
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Serotonin Antagonists / chemistry
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Serotonin Antagonists / pharmacology*
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Thiazoles / chemistry
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Thiazoles / pharmacology*
Substances
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Antipsychotic Agents
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Phosphatidylinositols
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Piperazines
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Receptors, Adrenergic
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Receptors, Dopamine
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Serotonin Antagonists
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Thiazoles
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Amphetamine
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Clozapine
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Apomorphine
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Dopamine
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Prazosin