How Do P2X3 Antagonists Work?

Reviewed on 10/5/2021

How Do P2X3 Antagonists Work?

P2X3 antagonists are a novel class of medications being developed to treat refractory or unexplained chronic cough. Currently, gefapixant, the first P2X3 antagonist, has progressed to phase-III clinical trials and awaits approval from the FDA.

P2X3 receptors are ion channels on the membranes of nerve cells (neurons) that allow the passage of ions in and out of neurons, when stimulated by a chemical known as adenosine triphosphate (ATP). P2X3 receptors are predominantly found on the sensory C fibers of the vagus nerve in the airway.

The airway lining cells release ATP in response to inflammation, irritation or injury to the airway. The cough reflex is stimulated when the released ATP binds to P2X3 receptors on the airway nerve fibers and initiates action within the neurons.

P2X3 antagonists prevent cough by binding to P2X3 receptors and preventing ATP from stimulating them. Studies suggest that P2X3 reduces the severity and frequency of cough in adult patients with chronic cough, and improves their quality of life.

How Are P2X3 Antagonists Used?

P2X3 antagonists are oral tablets being developed to treat:

  • Refractory chronic cough that persists despite appropriate treatment
  • Unexplained chronic cough whose underlying cause cannot be pinpointed despite evaluations


What Are Side Effects of P2X3 Antagonists?

Complete information on side effects of P2X3 antagonists is not available, however, a review of phase-II and phase-III randomized controlled trials indicates that the side effects (dose dependent) may include the following:

Taste disorders such as:

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

What Are Names of P2X3 Antagonist Drugs?

The generic name of P2X3 antagonist awaiting FDA approval is:

  • gefapixant



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