The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor.
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.
Jordan
Shaun
S
Neuroscience Department, Maryland Research Laboratories, Otsuka Maryland Research Institute, 9900 Medical Center Drive, Rockville, MD 20850, USA. shaunj@otsuka.com
Koprivica
Vuk
V
Chen
Ruoyan
R
Tottori
Katsura
K
Kikuchi
Tetsuro
T
Altar
C Anthony
CA
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000494:pharmacology; D000068180:Aripiprazole; D001665:Binding Sites / Q000502:physiology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology; D015363:Quinolones / Q000378:metabolism* / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000378:metabolism* / Q000494:pharmacology
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D000068180:Aripiprazole