Selective D1- and D2-dopamine receptor blockade both induces akathisia in humans--a PET study with [11C]SCH 23390 and [11C]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 micrograms. Akathisia, the syndrome of motor restlessness, appeared after the three highest doses. The akathisia was transient and occurred only when [11C]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 [11C]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 [11C]raclopride binding in the basal ganglia. The findings for [11C]raclopride and [11C]SCH 23390 are the first demonstration of a relationship between time courses for radioligand binding in the human brain and simultaneously induced pharmacological effects.
Farde
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Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden.
D000293:Adolescent; D000328:Adult; D017109:Akathisia, Drug-Induced; D001552:Benzazepines / Q000378:metabolism; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging; D018492:Dopamine Antagonists; D005260:Female; D006801:Humans; D008297:Male; D011595:Psychomotor Agitation / Q000000981:diagnostic imaging / Q000378:metabolism; D011699:Putamen / Q000000981:diagnostic imaging; D020891:Raclopride; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism; D013997:Time Factors; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride