Oral administration of NNC 756 — a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man

NNC 756 is a new benzazepine with high affinity and selectivity for D₁-dopamine receptors. In a double-blind, placebo controlled, cross-over study, positron emission tomography and the radioligand ¹¹C]SCH 23390 were used to determine central D₁-do-pamine receptor occupancy after a single oral dose of 80 mg NNC 756 in three healthy men. NNC 756 induced 75, 66 and 47% occupancy of D₁-dopamine receptors in the putamen of at 1.5 h after drug administration and 46, 36 and 24% after 7.5 h. There was a hyperbolic relationship between the occupancy values and the serum concentrations. The K_i value for the hyperbola was 6.4 ng/ml (±SD 1.4). The occupancy at 1.5 h is on the same level as that shown to induce effects in animal models for prediction of antipsychotic effect. Restlessness (akathisia) appeared in two subjects and nausea in one subject at time of peak drug concentration in serum. The oral dose level of 80 mg should be appropriate to investigate the potential antipsychotic effect of NNC 756.