The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor

Eur J Pharmacol. 2002 Apr 26;441(3):137-40. doi: 10.1016/s0014-2999(02)01532-7.

Abstract

Aripiprazole, 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy]-3,4-dihydro-2(1H)-quinolinone, a novel antipsychotic with partial agonist activity at dopamine D2 receptors, bound with high affinity to recombinant human 5-HT(1A) receptors (h5-HT(1A)) in Chinese hamster ovary cell membranes and displayed potent, partial agonism at 5-HT(1A) receptors in a guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTP gamma S)-binding assay that was blocked completely by a selective 5-HT(1A) receptor antagonist. An interaction with 5-HT(1A) receptors may contribute to the overall efficacy of aripiprazole against symptoms of schizophrenia, including anxiety, depression, cognitive and negative symptoms, and to its favorable side-effect profile. Combined with previous studies demonstrating the potent partial agonism of aripiprazole at dopamine D2 receptors, this study suggests aripiprazole is the first dopamine-serotonin system stabilizer.

MeSH terms

  • Animals
  • Antipsychotic Agents / metabolism*
  • Antipsychotic Agents / pharmacology
  • Aripiprazole
  • Binding Sites / physiology
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Humans
  • Piperazines / metabolism*
  • Piperazines / pharmacology
  • Quinolones / metabolism*
  • Quinolones / pharmacology
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / metabolism*
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Antipsychotic Agents
  • Piperazines
  • Quinolones
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Aripiprazole