The deuterated pyrazoloquinolinone targeting α6 subunit-containing GABA_A receptor as novel candidate for inhibition of trigeminovascular system activation: implication for migraine therapy.

ABSTRACT:

Introduction

The α6 subunit-containing GABA_A receptors (α6GABA_ARs) are highly expressed in the trigeminal ganglia (TG), the sensory hub of the trigeminovascular system (TGVS). Hypo-GABAergic transmission in the TG was reported to contribute to migraine-related behavioral and histopathological phenotypes. Previously, we found that Compound 6, an α6GABA_AR-selective positive allosteric modulator (PAM), significantly alleviated TGVS activation-induced peripheral and central sensitization in a capsaicin-induced migraine-mimicking model.

Methods

Here, we tested whether the deuterated analogues of Compound 6, namely DK-1-56-1 and RV-I-29, known to have longer half-lives than the parent compound, can exert a similar therapeutic effect in the same mod

SUBMITTER: Fan PC 

PROVIDER: S-EPMC11381949 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature