Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine
Article first published online: 22 MAY 2009
© 2009 The Authors. Journal compilation © 2009 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences
Volume 63, Issue 4, pages 529–537, August 2009
How to Cite
Tuppurainen, H., Kuikka, J. T., Viinamäki, H., Husso, M. and Tiihonen, J. (2009), Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine. Psychiatry and Clinical Neurosciences, 63: 529–537. doi: 10.1111/j.1440-1819.2009.01982.x
- Issue published online: 16 JUL 2009
- Article first published online: 22 MAY 2009
- Received 3 October 2008; revised 16 February 2009; accepted 24 Febrary 2009.
- receptor occupancy;
Aims: Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D2 receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D2/3 receptor apparent binding potential (BPapp) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients.
Methods: Dopamine D2/3 binding was studied on single-photon emission computed tomography ligand [123I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls.
Results: Statistically significant differences in midbrain dopamine D2/3 receptor BPapp (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used.
Conclusion: Both typical and second-generation antipsychotics occupy cortical dopamine D2/3 receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D2/3 occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.