BL-1020, a novel antipsychotic candidate with GABA-enhancing effects: D2 receptor occupancy study in humans

BL-1020 is a potentially novel antipsychotic, which comprises the typical antipsychotic perphenazine linked by an ester bound to γ-aminobutyric acid (GABA), intending a simultaneous dopamine-2 (D2) receptor blockade and GABA facilitation in the brain. This positron emission tomography (PET) study, using [11C]raclopride, assessed the extent and duration of D2 receptor occupancy (D2 RO) and safety for single doses of BL-1020 in healthy male subjects. Overall, this study did not raise any safety concern. Single doses of 16–32 mg BL-1020 caused a dose dependent striatal D2 RO. The 32 mg dose of BL-1020 resulted in an average D2 RO of 44% at 4–6 h post dosing (pd), which declined to 33% at 24 h pd. Equimolar doses of BL-1020 and perphenazine resulted in similar D2 RO at 24 h pd. Pharmacokinetic–pharmacodynamic analysis predicted that oral once daily administration of 32 mg BL-1020 would result in D2 ROs ranging from 52 to 66% at a steady state.