Pharmacological characterization of a novel potent, selective, and orally active orexin 2 receptor antagonist, SDM-878.

ABSTRACT:

Aims

Recently, we identified a novel orexin 2 (OX₂ ) receptor antagonist, SDM-878 (2-(3-(2-(1H-pyrazol-1-yl)nicotinoyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-3-methoxyisonicotinonitrile). The purpose of the present study is to characterize the in vitro and in vivo pharmacological effects of SDM-878.

Methods

The in vitro potency and selectivity of SDM-878 were examined in CHO cells that exhibit stable expression of human orexin 1 (OX₁ ), human orexin 2 (OX₂ ), rat OX₁ , and rat OX₂ receptors. Then, the plasma half-life, oral bioavailability, and brain penetration of SDM-878 were examined in rats. The in vivo effect of SDM-878 in rats was tested using electroencephalography (EEG). The target engagement of SDM-878 in the rat b

SUBMITTER: Maehara S 

PROVIDER: S-EPMC7722660 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature