PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement

LB-102 (N-methyl amisulpride) is tested in healthy volunteers to measure how long it occupies striatal dopamine D2/3 receptors, using PET with 11C raclopride. The study administers oral doses of 50, 75, and 100 mg either as single doses or as once-daily dosing to reach steady state, then samples receptor occupancy over about 24 hours. LB-102 dosing produced dopamine receptor occupancy in the desired 60-80% range at 50 mg across 24 hours. A key finding is that peak receptor occupancy substantially lags peak plasma concentration and shows little variability at steady state, which is contrary to the commonly observed plasma concentration versus receptor occupancy relationship. The trial is reported as generally safe and well tolerated, and the resulting occupancy timing data is used to support and inform dosing for a subsequent Phase 2 schizophrenia study.