1-Naphthylpiperazine Derivatives as Potential Atypical Antipsychotic Agents

J Med Chem. 1991 Jun;34(6):1860-6. doi: 10.1021/jm00110a016.

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

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Amphetamines / pharmacology
  • Animals
  • Antipsychotic Agents*
  • Apomorphine / pharmacology
  • Autoradiography
  • Behavior, Animal / drug effects
  • Dopamine Antagonists
  • Haloperidol / pharmacology
  • Ketanserin / metabolism
  • Locomotion / drug effects
  • Male
  • Piperazines / pharmacology*
  • Prazosin / metabolism
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / metabolism

Substances

  • Amphetamines
  • Antipsychotic Agents
  • Dopamine Antagonists
  • Piperazines
  • Tetrahydronaphthalenes
  • 1-(1-naphthyl)piperazine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Ketanserin
  • Haloperidol
  • Apomorphine
  • Prazosin