GABA_A receptor occupancy by subtype selective GABA_Aα2,3 modulators: PET studies in humans.

ABSTRACT:

Rationale

Sedation, dependence, and abuse liability limit the use of non-selective γ-aminobutyric acid (GABA_A) receptor positive modulators for the treatment of anxiety. AZD7325 and AZD6280 are novel, subtype-selective GABA_Aα2,3 receptor positive modulators with limited sedative effects.

Objectives

The current study aimed to confirm target engagement at GABA_A receptors by AZD7325 and AZD6280 in humans and to determine the relationship between exposure, GABA_A receptor occupancy, and tolerability.

Method

Two PET studies, using high-resolution research tomography (HRRT) and the radioligand [¹¹C]flumazenil, were performed in 12 subjects at baseline and after administration of single oral doses of AZD7325 (0.2 to 30 mg

SUBMITTER: Jucaite A 

PROVIDER: S-EPMC5263201 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature