Authors
Rajkumar Verma, Jinting Zhang, Sanjeev Kumar Yadav, Jianlin Feng, Chunxia C Cronin, Daylin Gamiotea-Turro, Kiran S Toti, Zhiwei Wen, Kenneth A Jacobson, Bruce T Liang
Published in
Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents. Apr 25, 2026. Epub Apr 25, 2026.
Abstract
Ischemic injury triggers extracellular ATP release, activating P2X4 receptors (P2 × 4R) on immune and cardiac cells, which exacerbates inflammation and tissue damage. We evaluated MRS4719, a selective P2 × 4R antagonist, in aged mice subjected to transient middle cerebral artery occlusion (tMCAo) and cardiac ischemia/reperfusion (CI/R) injury. MRS4719 exhibited a nonlinear dose response, with an intermediate dose (2.25 mg/kg/day) and short-term treatment (2 days) optimally improving sensorimotor and cognitive recovery while reducing brain tissue atrophy. Treatment initiated up to 12 h post-stroke significantly decreased infarct volume. Additionally, MRS4719 preserved cardiac contractile function following ischemia/reperfusion injury. These findings suggest that targeted P2X4R inhibition mitigates inflammatory injury across multiple organs and supports functional recovery, highlighting MRS4719's therapeutic potential for cerebral and cardiac ischemic disorders.
PMID:
42446538
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.
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