Dataset Information

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 tests, cytotoxicity was evaluated at three cell lines (neuroblastoma, astrocytes, and human peripheral blood mononuclear cells), and a neuroprotective effect was observed in rotenone-induced toxicity. In vivo experiments in a mouse neuropathic pain model demonstrated the highest analgesic effects of AR71 at the dose of 20 mg/kg body weight. Additionally, AR71 showed antiproliferative activity in higher concentrations. These findings suggest the need for further evaluation of AR71's therapeutic potential in treating ND and CNS cancer using animal experimental models.

SUBMITTER: Stasiak A

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

REPOSITORIES: biostudies-literature

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Publications

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

Stasiak Anna A Honkisz-Orzechowska Ewelina E Gajda Zbigniew Z Wagner Waldemar W Popiołek-Barczyk Katarzyna K Kuder Kamil J KJ Latacz Gniewomir G Juszczak Michał M Woźniak Katarzyna K Karcz Tadeusz T Szczepańska Katarzyna K Jóźwiak-Bębenista Marta M Kieć-Kononowicz Katarzyna K Łażewska Dorota D

International journal of molecular sciences 20240723 15

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 (Ki = 24 nM) and selectivity towards histamine H1 and H4 receptors (Ki > 2500 nM), and showed anti-inflammatory activity in a m ...[more]

PMID: 39125607

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Dataset Information

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

Publications

AR71, Histamine H<sub>3</sub> Receptor Ligand-In Vitro and In Vivo Evaluation (Anti-Inflammatory Activity, Metabolic Stability, Toxicity, and Analgesic Action).

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