POSITRON EMISSION TOMOGRAPHIC ANALYSIS OF CENTRAL DOPAMINE D-1 RECEPTOR-BINDING IN NORMAL SUBJECTS TREATED WITH THE ATYPICAL NEUROLEPTIC, SDZ MAR-327

SDZ MAR 327 is a new neuroleptic agent with high in vitro affinity for dopamine D-1 and D-2 receptors. The goal of this study was to determi ne the effect of time after SDZ MAR 327 administration on central dopa mine D-1 receptor occupancy in healthy humans. Positron emission tomog raphy (PET) with the dopamine D-1 receptor ligand, [C-11] SCH 23390, w as performed in 6 male volunteers (age 22-34), in both the drug naive state and at 1, 2 and 4 h after a single oral dose of SDZ MAR 327 (9 m g). The pre and post drug treatment [C-11] SCH 23390 dynamic data were analyzed using two different methods, each yielding a parameter propo rtional to the receptor density: i) a simple regional comparison appro ximating the specifically bound to free fraction, B/F; and ii) a two c ompartment, two parameter model yielding the apparent distribution vol ume DV''. With both methods, a metabolite corrected arterial input fun ction was used and the vascular fraction of tissue (V-b) was fixed at a previously determined value of 4%. Method I served as a qualitative comparison of the paired studies and demonstrated little difference be tween the pre and post drug conditions, method II also confirmed that there was no significant change in binding of [C-11] SCH 23390 in the striatum. These data indicate that SDZ MAR 327 produces little if any effect on dopamine D-1 receptor binding at the dose used.