Application of the PET ligand [¹¹C]ORM-13070 to examine receptor occupancy by the α_2C-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain.

ABSTRACT:

Background

Availability of the α_2C-adrenoceptor (α_2C-AR) positron emission tomography (PET) tracer, [¹¹C]ORM-13070, and the α_2C-AR antagonist ORM-12741 allows probing of the roles of this G-protein coupled receptor subtype in brain function, both in healthy humans and in patients with various brain disorders. This translational study employed [¹¹C]ORM-13070 autoradiography and PET to determine α_2C-AR occupancy by ORM-12741 in rat and human brain, respectively.

Results

ORM-12741 has high affinity (K_i: 0.08 nM) and potent antagonist activity (K_b: 0.04 nM) as well as selectivity (K_i estimates for the human α_2A-AR and α_2B-AR were 8.3 nM and 0.8 nM, respectivel

SUBMITTER: Shahid M 

PROVIDER: S-EPMC7726058 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature