BL-1020, a novel antipsychotic candidate with GABA-enhancing effects: D-2 receptor occupancy study in humans

TY - JOUR

T1 - BL-1020, a novel antipsychotic candidate with GABA-enhancing effects: D-2 receptor occupancy study in humans

AU - Appel, Lieuwe

AU - Geffen, Yona

AU - Heurling, Kerstin

AU - Eriksson, Catarina

AU - Antoni, Gunnar

AU - Kapur, Shitij

PY - 2009/12

Y1 - 2009/12

N2 - BL-1020 is a potentially novel antipsychotic, which comprises the typical antipsychotic perphenazine linked by an ester bound to gamma-aminobutyric acid (GABA), intending a simultaneous dopamine-2 (D-2) receptor blockade and GABA facilitation in the brain. This positron emission tomography (PET) study, using [C-11]raclopride, assessed the extent and duration of D-2 receptor occupancy (D-2 RO) and safety for single doses of BL-1020 in healthy mate subjects. Overall, this study did not raise any safety concern. Single closes of 16-32 mg BL-1020 caused a dose dependent striatal D-2 RO. The 32 mg dose of BL-1020 resulted in an average D-2 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 D-2 RO at 24 h pd. Pharmacokinetic-pharmacodynamic analysis predicted that oral once daily administration of 32 mg BL-1020 would result in D-2 ROs ranging from 52 to 66% at a steady state. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.

AB - BL-1020 is a potentially novel antipsychotic, which comprises the typical antipsychotic perphenazine linked by an ester bound to gamma-aminobutyric acid (GABA), intending a simultaneous dopamine-2 (D-2) receptor blockade and GABA facilitation in the brain. This positron emission tomography (PET) study, using [C-11]raclopride, assessed the extent and duration of D-2 receptor occupancy (D-2 RO) and safety for single doses of BL-1020 in healthy mate subjects. Overall, this study did not raise any safety concern. Single closes of 16-32 mg BL-1020 caused a dose dependent striatal D-2 RO. The 32 mg dose of BL-1020 resulted in an average D-2 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 D-2 RO at 24 h pd. Pharmacokinetic-pharmacodynamic analysis predicted that oral once daily administration of 32 mg BL-1020 would result in D-2 ROs ranging from 52 to 66% at a steady state. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.

U2 - 10.1016/j.euroneuro.2009.07.009

DO - 10.1016/j.euroneuro.2009.07.009

M3 - Article

SN - 1873-7862

VL - 19

SP - 841

EP - 850

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 12

ER -