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.