Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

Journal Article · Fri Jan 01 00:00:00 EST 1988 · Arch. Gen. Psychiatr.; (United States)

DOI:https://doi.org/10.1001/archpsyc.1988.01800250087012· OSTI ID:5362297

Farde, L; Wiesel, F A; Halldin, C; Sedvall, G

Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.

• Research Organization: Karolinska Institute, Stockholm, Sweden
• OSTI ID: 5362297
• Journal Information: Arch. Gen. Psychiatr.; (United States), Vol. 45:1
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
DOPAMINE
RECEPTORS
NERVOUS SYSTEM DISEASES
DIAGNOSIS
PSYCHOTROPIC DRUGS
BIOLOGICAL EFFECTS
BRAIN
CARBON 11
LIGANDS
PATIENTS
POSITRON COMPUTED TOMOGRAPHY
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISEASES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
HYDROXY COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RADIOISOTOPES
SYMPATHOMIMETICS
TOMOGRAPHY
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