Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes

Cindy P. Lawler, Cassandra Prioleau, Mechelle M. Lewis, Chun Mak, Dong Jiang, John A. Schetz, Antonio M. Gonzalez, David R. Sibley, Richard B. Mailman

Research output: Contribution to journalArticlepeer-review

397 Scopus citations


OPC-14597 {aripiprazole; 7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone} is a novel candidate antipsychotic that has high affinity for striatal dopamine D2-like receptors, but causes few extrapyramidal effects. These studies characterized the molecular pharmacology of OPC-14597, DM-1451 (its major rodent metabolite), and the related quinolinone derivative OPC-4392 at each of the cloned dopamine receptors, and at serotonin 5HT6 and 5HT7 receptors. All three compounds exhibited highest affinity for D(2L) and D(2S) receptors relative to the other cloned receptors examined. Both OPC-4392 and OPC-14597 demonstrated dual agonist/antagonist actions at D(2L) receptors, although the metabolite DM-1451 behaved as a pure antagonist. These data suggest that clinical atypicality can occur with drugs that exhibit selectivity for D(2L)/D(2S) rather than D3 or D4 receptors, and raise the possibility that the unusual profile of OPC-14597 in vivo (presynaptic agonist and postsynaptic antagonist) may reflect different functional consequences of this compound interacting with a single dopamine receptor subtype (D2) in distinct cellular locales. Copyright (C) 1999 American College of Neuropsychopharmacology.

Original languageEnglish
Pages (from-to)612-627
Number of pages16
Issue number6
StatePublished - Jun 1999


  • Adenylyl cyclase
  • Antipsychotic
  • Aripiprazole
  • C-6 cells
  • CHO cells
  • Dopamine receptors
  • Functional selectivity
  • Schizophrenia


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