Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine.

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Tuppurainen H, Kuikka JT, Viinamaki H, Husso M, Tiihonen J

Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine.

Psychiatry Clin Neurosci. 2009 Aug;63(4):529-37. doi: 10.1111/j.1440-1819.2009.01982.x. Epub 2009 May 22.

PubMed ID

19496999 [ View in PubMed

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Abstract

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 D(2) receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D(2/3) receptor apparent binding potential (BP(app)) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients. METHODS: Dopamine D(2/3) binding was studied on single-photon emission computed tomography ligand [(123)I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naive patients and seven healthy controls. RESULTS: Statistically significant differences in midbrain dopamine D(2/3) receptor BP(app) (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-naive 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 D(2/3) receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D(2/3) occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Haloperidol	Dopamine D3 receptor	Protein	Humans	Unknown	Inverse agonist	Details