Gefapixant

Gefapixant is an allosteric antagonist of the purinergic P2X₃ receptor.¹ It inhibits agonist-induced P2X₃ and P2X_2/3 currents in 1321N1 cells co-expressing human P2X₂ and P2X₃ (IC₅₀s = 153 and 220 nM, respectively) but does not inhibit P2X₂ currents in the same cells at 10 µM. In vivo, gefapixant (30 mg/kg) increases the paw withdrawal threshold and decreases weight-bearing discomfort in a rat model of inflammatory hyperalgesia induced by complete Freund’s adjuvant (CFA) and a rat model of neuropathic pain induced by sciatic nerve injury. Gefapixant (10 mg/kg) improves cardiac function, reduces cardiac TNF-α levels, and prevents cardiac fibrosis in a rat model of myocardial infarction induced by left anterior descending (LAD) branch ligation.² Formulations containing gefapixant have been used in the treatment of chronic cough.

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1. Richards, D., Gever, J.R., Ford, A.P., et al. Action of MK‐7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br. J. Pharmacol. 176(13), 2279-2291 (2019).

2. Wei, Y.-Z., Yang, S., Li, W., et al. Gefapixant, a novel P2X3 antagonist, protects against post myocardial infarction cardiac dysfunction and remodeling via suppressing NLRP3 inflammasome. Curr. Med. Sci. 43(1), 58-68 (2023).