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

被引：10

作者：

Appel, Lieuwe ^{[1
]}

Geffen, Yona ^{[2
]}

Heurling, Kerstin ^{[1
]}

Eriksson, Catarina ^{[3
]}

Antoni, Gunnar ^{[1
]}

Kapur, Shitij ^{[4
]}

机构：

[1] GE Healthcare, Uppsala Imanet AB, Uppsala, Sweden

[2] BioLineRx Ltd, Jerusalem, Israel

[3] Phase I Serv, Quintiles AB, Uppsala, Sweden

[4] Kings Coll London, Inst Psychiat, Dept Psychol Med, London WC2R 2LS, England

来源：

EUROPEAN NEUROPSYCHOPHARMACOLOGY | 2009年 / 19卷 / 12期

关键词：

PET; Antipsychotics; Perphenazine; GABA; Dopamine-2; receptors; Schizophrenia; DOUBLE-BLIND PET; SCHIZOPHRENIC-PATIENTS; PERPHENAZINE; DOPAMINE; CORTEX; BRAIN; DRUGS; MODEL;

D O I：

10.1016/j.euroneuro.2009.07.009

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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.

引用

页码：841 / 850

页数：10

共 25 条

[1]

ANDERSSON JLR, 1995, J NUCL MED, V36, P657

[2]

DOPAMINE-IMMUNOREACTIVE AXON VARICOSITIES FORM NONRANDOM CONTACTS WITH GABA-IMMUNOREACTIVE NEURONS OF RAT MEDIAL PREFRONTAL CORTEX [J].