SELECTIVE D1-DOPAMINE AND D2-DOPAMINE RECEPTOR BLOCKADE BOTH INDUCES AKATHISIA IN HUMANS - A PET STUDY WITH [C-11] SCH-23390 AND [C-11] RACLOPRIDE

Pharmacological effects were recorded and time course for receptor binding in brain was followed by positron emission tomography after IV injection of the selective D1-dopamine receptor antagonist SCH 23390 in four healthy subjects in doses of 310-810-mu-g. Akathisia, the syndrome of motor restlessness, appeared after the three highest doses. The akathisia was transient and occurred only when [C-11]SCH 23390 binding in the basal ganglia was at a high level with a central D1-dopamine receptor occupancy of 45-59%. The D2-dopamine receptor antagonist [C-11]raclopride was injected IV into 20 healthy subjects and 13 schizophrenic patients. Akathisia appeared in 14 healthy subjects and 7 patients and coincided with maximal [C-11]raclopride binding in the basal ganglia. The findings for [C-11]raclopride and [C-11]SCH 23390 are the first demonstration of a relationship between time courses for radioligand binding in the human brain and simultaneously induced pharmacological effects.