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

• Published in: Psychiatry and clinical neurosciences Vol. 63; no. 4; pp. 529 - 537
• Main Authors: Tuppurainen, Heli, Kuikka, Jyrki T., Viinamäki, Heimo, Husso, Minna, Tiihonen, Jari
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.08.2009; Wiley-Blackwell
• Subjects: Adult; Adult and adolescent clinical studies; antipsychotic; Antipsychotic Agents - metabolism; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; Benzamides; Benzodiazepines - metabolism; Benzodiazepines - pharmacokinetics; Benzodiazepines - therapeutic use; Biological and medical sciences; Clozapine - metabolism; Clozapine - pharmacokinetics; Clozapine - therapeutic use; dopamine; epidepride; Female; Haloperidol - pharmacokinetics; Haloperidol - therapeutic use; Humans; Iodine Radioisotopes; Male; Medical sciences; Mesencephalon - diagnostic imaging; Mesencephalon - drug effects; Mesencephalon - metabolism; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Pyrrolidines; receptor occupancy; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3 - drug effects; Receptors, Dopamine D3 - metabolism; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - metabolism; Temporal Lobe - diagnostic imaging; Temporal Lobe - drug effects; Temporal Lobe - metabolism; Tomography, Emission-Computed, Single-Photon; Atypical antipsychotic; Olanzapine; epidepride; Neuroleptic; Psychotropic; Central nervous system; Pharmacotherapy; Schizophrenia; Serotonine receptor; Haloperidol; Encephalon; Psychosis; receptor occupancy; antipsychotic; Biological receptor; Dopamine; Dopamine receptor; Dopamine antagonist; Serotonin antagonist; Midbrain; Butyrophenone derivatives; Temporal cortex; Clozapine; Catecholamine; Thienobenzodiazepine derivatives; Treatment; D2 Dopamine receptor; Neurotransmitter
• ISSN: 1323-1316; 1440-1819
• DOI: 10.1111/j.1440-1819.2009.01982.x

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.