Dopamine autoreceptor agonists as potential antipsychotics. 2. (Aminoalkoxy)-4H-1-benzopyran-4-ones

J Med Chem. 1991 Jan;34(1):248-56. doi: 10.1021/jm00105a039.


The synthesis and pharmacological properties of a novel type of [(arylpiperazinyl)alkoxy]-4H-1-benzopyran-4-ones with dopaminergic activity are described. The nature of the arylpiperazine (AP) moiety determines the dopamine (DA) agonist/antagonist character of this series of compounds; when the aryl portion of the AP is unsubstituted the compounds appear to be DA autoreceptor agonists while substituted aryl groups seem to impart DA antagonist activity. A heterocyclic piperazine, 7-[3-[4-(2-pyridinyl)-1-piperazinyl]propoxy]-4H-1-benzopyran-4-one (31, PD 119819) has been identified as an extremely selective DA autoreceptor agonist in tests that include [3H]haloperidol binding, inhibition of spontaneous locomotor activity, inhibition of brain DA synthesis, inhibition of brain DA neuronal firing, stereotypy assessment, and reversal of 6-hydroxydopamine (6-OHDA) induced akinesia in rats. In addition, 31 possesses good oral activity in the Sidman avoidance test in squirrel monkeys, a predictor of clinical antipsychotic efficacy. In another primate model, 31 has been found to lack the liability for extrapyramidal side effects observed with currently available antipsychotic drugs.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antipsychotic Agents / chemical synthesis*
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology
  • Binding, Competitive
  • Brain / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology
  • Depression / drug therapy
  • Dopamine / biosynthesis
  • Dopamine Agents / chemical synthesis*
  • Haloperidol / metabolism
  • Indicators and Reagents
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects*
  • Neurons / drug effects
  • Neurons / physiology
  • Rats
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / physiology
  • Structure-Activity Relationship
  • Synapses / physiology


  • Antipsychotic Agents
  • Benzopyrans
  • Dopamine Agents
  • Indicators and Reagents
  • Receptors, Dopamine
  • Haloperidol
  • Dopamine