Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study.
The hypothesis that poor response to antipsychotic medication is due to inadequate occupancy of central D2 receptors was tested in vivo. We assessed striatal D2 dopamine receptor availability for binding with the specific ligand 123I IBZM by single photon emission tomography (SPET) in two groups of DSM-III-R diagnosed schizophrenic patients on typical antipsychotic medication, and a group of healthy controls (N = 20). Patients were characterized by clinical ratings as antipsychotic responders (N = 10) or non-responders (N = 8). Dynamic single slice SPET, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq 123I IBZM. Semiquantitative analysis generated indices of D2 receptor availability for binding. There was no difference in striatal D2 receptor availability between the patient groups, both showing a similar degree of occupancy by antipsychotic medication compared to the control group. Thus, poor clinical response does not appear to be accounted for by differential blockade, or inadequate occupancy of striatal dopamine D2 receptors by antipsychotic medication.
Pilowsky
L S
LS
Institute of Psychiatry, Genetics Section, De Crespigny Park, London.
Costa
D C
DC
Ell
P J
PJ
Murray
R M
RM
Verhoeff
N P
NP
Kerwin
R W
RW
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011569:Psychiatric Status Rating Scales; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide