[I-123] IBZM SPECT IN PATIENTS TREATED WITH TYPICAL AND ATYPICAL NEUROLEPTICS - RELATIONSHIP TO DRUG PLASMA-LEVELS AND EXTRAPYRAMIDAL SIDE-EFFECTS

[I-123]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor lig and and can be used to visualize brain D-2 receptors in humans with si ngle photon emission computerized tomography (SPECT). The ratio of str iatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D, receptor binding in the striatum. Ou r study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscula rly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical n euroleptics (TNs) and atypical neuroleptics (ANs) were significantly d ifferent in their ST/FC ratios. The ST/FC ratios indicated that patien ts treated with benperidol exhibited the lowest ST/FC ratios, with inc reasingly higher ratios in patients on haloperidol or clozapine. We fo und a curvilinear relationship between the ST/FC ratios and the dose/k g body wt. of TNs and ANs on the basis of a dose-normalization accordi ng to K-i-values of the neuroleptic at D-2 receptors and a weaker, but also curvilinear relationship between ST/FC ratios and normalized dos ages according to clinically defined chlorpromazine equivalents. The s pecific uptake of IBZM did not correlate with the plasma levels of the TN haloperidol at the present dose range (0-12.4 ng/ml). For clozapin e, a meaningful negative correlation between plasma levels and ST/FC r atio could be established. There was a negative continuous correlation between uptake of IBZM and extrapyramidal side effects, which is diff erent from the threshold-based relationship between extrapyramidal sid e effects and IBZM uptake reported previously. (C) 1997 Elsevier Scien ce Ireland Ltd.