The D-2 receptor occupancy profile of loxapine determined using PET

Position emission tomography (PET) studies of typical neuroleptics suggest that 60% to 80% of striatal D-2 occupancy may be sufficient for optimal clinical treatment of psychosis. Therefore, striatal D-2 occupancy may be used as an index to determine the optimal dose range. Toward this end, we determined the in vivo D-2 profile of loxapine, using [C-11]-raclopride and PET. Seven patients selected from a clinical population were scanned while taking steady-state oval loxapine from 10 to 100 mg/day. Their D-2 receptor occupancy was estimated by comparing them to age-matched data from neuroleptic-naive patients. The O-2 receptor occupancy ranged from 52% to 90%, and there was a very strong relationship between dose and O-2 occupancy, suggesting that 15 to 30 mg/day of loxapine would produce, the putatively optimal, 60% to 80% striatal D-2 blockade. This dose range is much lower than that used in most clinical settings and points to the potential efficacy of loxapine at lower closes. (C) 1996 American College of Neuropsychopharmacology