RATIONALE: Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D₂ receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D₂ receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D₂ receptors have reported inconsistent results regarding regional differences of dopamine D₂ receptor occupancy by aripiprazole. OBJECTIVE: To test the hypothesis of preferential binding to extrastriatal dopamine D₂ receptors by aripiprazole, we investigated its regional dopamine D₂ receptor occupancies in healthy young subjects. MATERIALS AND METHODS: Using PET and two radioligands with different affinities for dopamine D₂ receptors, [¹¹C]raclopride and [¹¹C]FLB457, striatal and extrastriatal dopamine D₂ receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy subjects. RESULTS: Our data showed that dopamine D₂ receptor occupancies in the striatum measured with [¹¹C]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [¹¹C]FLB457 ranging from 46.6% to 58.4%. CONCLUSIONS: In the present study, preferential extrastriatal dopamine D₂ receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D₂ receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.
RATIONALE: Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D₂ receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D₂ receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D₂ receptors have reported inconsistent results regarding regional differences of dopamine D₂ receptor occupancy by aripiprazole. OBJECTIVE: To test the hypothesis of preferential binding to extrastriatal dopamine D₂ receptors by aripiprazole, we investigated its regional dopamine D₂ receptor occupancies in healthy young subjects. MATERIALS AND METHODS: Using PET and two radioligands with different affinities for dopamine D₂ receptors, [¹¹C]raclopride and [¹¹C]FLB457, striatal and extrastriatal dopamine D₂ receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy subjects. RESULTS: Our data showed that dopamine D₂ receptor occupancies in the striatum measured with [¹¹C]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [¹¹C]FLB457 ranging from 46.6% to 58.4%. CONCLUSIONS: In the present study, preferential extrastriatal dopamine D₂ receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D₂ receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.
Authors: V Bigliani; R S Mulligan; P D Acton; D Visvikis; P J Ell; C Stephenson; R W Kerwin; L S Pilowsky Journal: Br J Psychiatry Date: 1999-09 Impact factor: 9.319
Authors: Robert M Kessler; M Sib Ansari; Patrizia Riccardi; Rui Li; Karuna Jayathilake; Benoit Dawant; Herbert Y Meltzer Journal: Neuropsychopharmacology Date: 2006-05-31 Impact factor: 7.853
Authors: Paul W Czoty; H Donald Gage; Pradeep K Garg; Sudha Garg; Michael A Nader Journal: Psychopharmacology (Berl) Date: 2013-09-29 Impact factor: 4.530
Authors: Xenia M Hart; Christoph Hiemke; Luzie Eichentopf; Xenija M Lense; Hans Willi Clement; Andreas Conca; Frank Faltraco; Vincenzo Florio; Jessica Grüner; Ursula Havemann-Reinecke; Espen Molden; Michael Paulzen; Georgios Schoretsanitis; Thomas G Riemer; Gerhard Gründer Journal: Psychopharmacology (Berl) Date: 2022-10-05 Impact factor: 4.415
Authors: Charles R Conway; John T Chibnall; Paul Cumming; Mark A Mintun; Marie Anne I Gebara; Dana C Perantie; Joseph L Price; Martha E Cornell; Jonathan E McConathy; Sunil Gangwani; Yvette I Sheline Journal: Psychiatry Res Date: 2014-01-14 Impact factor: 3.222
Authors: Anna Murphy; Serdar Dursun; Shane McKie; Rebecca Elliott; John Francis William Deakin Journal: Psychopharmacology (Berl) Date: 2016-02-22 Impact factor: 4.530