Quantification of neuroreceptors in living human brain. v. endogenous neurotransmitter inhibition of haloperidol binding in psychosis.
The half-inhibition concentration (IC50) of a drug indicates its ability to inhibit the binding of other ligands of a receptor. The authors used positron emission tomography to test the hypothesis that haloperidol's IC50 toward the binding of tracer N-[11C]methylspiperone ([11C]NMSP) in brain must be increased in patients in whom more dopamine is bound to receptors than in healthy volunteers. The IC50 of haloperidol was significantly elevated from 1.5 nmol/L in healthy volunteers and patients with bipolar disease without psychosis to 4.5 nmol/L in patients with schizophrenia or bipolar disease with psychosis. The higher IC50 values in psychosis are consistent with an 8-fold increased binding of dopamine and a 16-fold elevated concentration of synaptic dopamine in psychosis. At the 80% haloperidol blockade of the receptors, the calculated amount of neurotransmitter bound in the patients with psychosis declined to twice the value estimated in the nonpsychotic subjects, that is, 5 pmol cm(-3).
Gjedde
A
A
Positron Emission Tomography Center, Aarhus University Hospitals, Aarhus, Denmark.
Wong
D F
DF
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006220:Haloperidol / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009716:Numerical Analysis, Computer-Assisted; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000378:metabolism*
D014150:Antipsychotic Agents; D006220:Haloperidol