AR71, Histamine H₃ Receptor Ligand-In Vitro and In Vivo Evaluation (Anti-Inflammatory Activity, Metabolic Stability, Toxicity, and Analgesic Action).

ABSTRACT: The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity for human H₃R (K_i = 24 nM) and selectivity towards histamine H₁ and H₄ receptors (K_i > 2500 nM), and showed anti-inflammatory activity in a model of lipopolysaccharide-induced inflammation in BV-2 cells. The presented tests confirmed its antagonist/inverse agonist activity profile and good metabolic stability while docking studies showed the binding mode to histamine H₁, H₃, and H₄ receptors. In in vitro

SUBMITTER: Stasiak A 

PROVIDER: S-EPMC11311998 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature