Abstract
The design and synthesis of a series of potential atypical antipsychotic agents based on the structure of 1-naphthylpiperazine are described. The incorporation of dopamine antagonist activity into the parent structure was achieved with heterocyclic surrogates for the catechol moiety of dopamine. Compound 4b from this series showed a biochemical profile that translated to behavioral activity in the rat predictive of an antipsychotic agent with a low propensity to cause extrapyramidal side effects in man.
MeSH terms
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Amphetamines / pharmacology
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Animals
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Antipsychotic Agents*
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Apomorphine / pharmacology
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Autoradiography
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Behavior, Animal / drug effects
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Dopamine Antagonists
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Haloperidol / pharmacology
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Ketanserin / metabolism
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Locomotion / drug effects
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Male
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Piperazines / pharmacology*
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Prazosin / metabolism
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Rats
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Rats, Inbred Strains
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Structure-Activity Relationship
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Tetrahydronaphthalenes / metabolism
Substances
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Amphetamines
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Antipsychotic Agents
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Dopamine Antagonists
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Piperazines
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Tetrahydronaphthalenes
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1-(1-naphthyl)piperazine
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Ketanserin
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Haloperidol
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Apomorphine
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Prazosin