Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABA_A Receptor Modulators.

ABSTRACT: We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α₄β₃γ₂ GABA_AR selective compound 1 and acidic α₅β₃γ₂ selective GABA_AR positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compounds 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties. Additionally, compound 1 reduced the number of lung CD4⁺ T lymphocytes and direc

SUBMITTER: Forkuo GS 

PROVIDER: S-EPMC5497587 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature