TRPM8 Channel Agonists

TRPM8 channel agonists are a new class of drugs that help relieve dry eye disease (DED) by stimulating natural tear production. They work by activating cold-sensitive receptors on the eye’s surface, helping reduce dryness and discomfort. 

DED, also known as keratoconjunctivitis sicca, is a common ocular surface disorder caused by reduced tear production or excessive tear evaporation. It leads to tear film instability, inflammation, and damage to the eye’s surface. Symptoms may include dryness, burning, a gritty sensation, and blurry vision. In DED, changes in nerve sensitivity may impair the eye’s ability to sense dryness and trigger tear production.

TRPM8 receptors are cold-sensitive sensors located on branches of the trigeminal nerve, which supplies the cornea and eyelids. These receptors help detect dryness and temperature changes on the eye’s surface, and send signals through the trigeminal nerve to stimulate tear production. In DED, this sensory response may be reduced, leading to fewer natural tears and more discomfort. TRPM8 agonists work by activating these receptors to help restore natural tear flow. They can also produce a mild cooling sensation that helps soothe symptoms such as dryness and irritation.

The first and only TRPM8 channel agonist approved to treat dry eye disease is acoltremon ophthalmic solution 0.003% (Tryptyr). Approved by the FDA on May 28, 2025, Tryptyr is expected to become available in the U.S. in the third quarter of 2025.

TRPM8 channel agonists are used to treat dry eye disease. The first approved drug in this class is available as an ophthalmic solution in single-use vials. The recommended dose is one drop in each eye, twice daily.

Common side effects of TRPM8 channel agonists include the following:

• Instillation site pain

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.

Generic and brand names of FDA-approved TRPM8 channel agonists include:

• Tryptyr
• acoltremon