Internal medicine

Biotechnology

Nociception

Neuroscience

Receptor

In vivo

Biology

Patch clamp

Chemistry

Receptor antagonist

Antagonist

Hyperalgesia

Ion channel

Medicine

Pharmacology

British Journal of Pharmacology

The P2X3 receptor is an ATP-gated ion channel expressed by sensory afferent neurons and is used as a target to treat chronic sensitisation conditions. The first-in-class, selective P2X3 and P2X2/3 receptor antagonist, the diaminopyrimidine MK-7264 (gefapixant), has progressed to Phase III trials for refractory or unexplained chronic cough. We used patch clamp to elucidate the pharmacology and kinetics of MK-7264 and rat models of hypersensitivity and hyperalgesia to test its efficacy on these conditions.

Action of MK‐7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation