Trial reportBMC ophthalmology2017
A novel TRPM8 agonist relieves dry eye discomfort.
Trial report in BMC ophthalmology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Infraorbital Skin Application of Menthol Emulsion for Dry Eye Disease: A Randomized Clinical Trial.Ophthalmology and therapy · 2026Article
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels.Current issues in molecular biology · 2026Review
- Cold- and TRPM8-dependent shaking in mammals and birds.Communications biology · 2025Article
- Acoltremon and the TRPM8 frontier: a new chapter in dry eye disease therapy.Annals of medicine and surgery (2012) · 2025Article
- Thermosensitive TRP Channels Are Functionally Expressed and Influence the Lipogenesis in Human Meibomian Gland Cells.International journal of molecular sciences · 2024Article
- Multidimensional immunotherapy for dry eye disease: current status and future directions.Frontiers in ophthalmology · 2024Review
- Review
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- Trigeminal Function in Sino-Nasal Health and Disease.Biomedicines · 2023Review
- "ThermoTRP" Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist).International journal of molecular sciences · 2023Review
- Ion channels in dry eye disease.Indian journal of ophthalmology · 2023Review
- Molecular determinants of TRPM8 function: key clues for a cool modulation.Frontiers in pharmacology · 2023Review
- Ocular Surface Ion Transport and Dry Eye Disease.Current ophthalmology reports · 2022Article
- Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands.Medicinal research reviews · 2022Review
- Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIPScience (New York, N.Y.) · 2022Article
- Involvement of transient receptor potential channels in ocular diseases: a narrative review.Annals of translational medicine · 2022Article
- The contribution of ion channels to shaping macrophage behaviour.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundPhysical cooling of the eye surface relieves ocular discomfort, but translating this event to drug treatment of dry eye discomfort not been studied. Here, we synthesized a water-soluble TRPM8 receptor agonist called cryosim-3 (C3, 1-diisopropylphosphorylnonane) which selectively activates TRPM8 (linked to cooling) but not TRPV1 or TRPA1 (linked to nociception) and tested C3 in subjects with mild forms of dry eye disease.
methodsA set of 1-dialkylphosphoryalkanes were tested for activation of TRPM8, TRPV1 and TRPA1 receptors in transfected cells. The bioactivity profiles were compared by perioral, topical, and intravenous delivery to anesthetized rats. The selected lead candidate C3 or vehicle (water) was applied with a cotton gauze pad to upper eyelids of patients with dry eye disease (n = 30). Cooling sensation, tear film break-up time (TBUT), basal tear secretion, and corneal staining were evaluated. C3 was then applied four times daily for 2 weeks to patients using a pre-loaded single unit applicator containing 2 mg/mL of C3 in water (n = 20) or water only. TBUT, basal tear secretion, and corneal staining, and three questionnaires surveys of ocular discomfort (VAS scale, OSDI, and CVS symptoms) were analyzed before and at 1 and 2 weeks thereafter.
resultsC3 was a selective and potent TRPM8 agonist without TRPV1 or TRPA1 activity. In test animals, the absence of shaking behavior after C3 perioral administration made it the first choice for further study. C3 increased tear secretion in an animal model of dry eye disease and did not irritate when wiped on eyes of volunteers. C3 singly applied (2 mg/ml) produced significant cooling in <5 min, an effecting lasting 46 min with an increase in tear secretion for 60 min. C3 applied for 2 weeks also significantly increased basal tear secretion with questionnaire surveys of ocular discomfort indices clearly showing improvement of symptoms at 1 and 2 weeks. No complaints of irritation or pain were reported by any subject.
conclusionsC3 is a promising candidate for study of TRPM8 function on the eye surface and for relief of dry eye discomfort.
trial registrationISRCTN24802609 and ISRCTN13359367 . Registered 23 March 2015 and 2 September 2015.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.