Acoltremon

Acoltremon
	molecular structure
	3D representation
Clinical data
Trade names	Tryptyr
Other names	AVX-012, WS-12
License data	US DailyMed: Acoltremon;
ATC code	None;
Legal status
Legal status	US: ℞-only;
Identifiers
	IUPAC name (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide;
CAS Number	68489-09-8;
PubChem CID	11266244;
DrugBank	DB19202;
ChemSpider	9441255;
UNII	1L7BVT4Z4Z;
ChEMBL	ChEMBL2441929;
CompTox Dashboard (EPA)	DTXSID10460636 ;
Chemical and physical data
Formula	C18H27NO2
Molar mass	289.419 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C;
	InChI InChI=1S/C18H27NO2/c1-12(2)16-10-5-13(3)11-17(16)18(20)19-14-6-8-15(21-4)9-7-14/h6-9,12-13,16-17H,5,10-11H2,1-4H3,(H,19,20)/t13-,16+,17-/m1/s1; Key:HNSGVPAAXJJOPQ-XOKHGSTOSA-N;

Acoltremon sold under the brand name Tryptyr, is a medication used for the treatment of dry eye syndrome.^[1]

Medical uses

Acoltremon was approved for medical use in the United States in May 2025 or the treatment of signs and symptoms associated with dry eye disease.^[2]^[3] Alcon anticipates launching the product in the U.S. during the third quarter of 2025.^[4]

Pharmacology

Acoltremon acts as a potent and selective activator (opener) of the TRPM8 calcium channel, which is responsible for the sensation of coldness produced by menthol (of which acoltremon is a chemical analogue of). ^[5] It is slightly less potent as a TRPM8 activator compared to icilin, but is much more selective for TRPM8 over related calcium channels.^[6]

Animal studies

It produces analgesic and anti-inflammatory effects in animal models with similar efficacy to menthol and a reduced side effect profile.^[7]^[8]^[9]^[10]^[11]

Clinical trials

Although the precise mechanism in treating dry eye remains unclear, Phase 3 clinical trials showed that a greater proportion of patients using acoltremon experienced increased tear production compared to those using a placebo.^[12]

References

^ "Acoltremon - Alcon". AdisInsight. Springer Nature Switzerland AG.
^ "Novel Drug Approvals for 2025". U.S. Food and Drug Administration (FDA). 29 May 2025. Retrieved 29 May 2025.
^ "Alcon Announces FDA Approval of Tryptyr (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease" (Press release). Alcon. 28 May 2025. Retrieved 29 May 2025 – via Business Wire.
^ "FDA approves Tryptyr to treat dry eye signs, symptoms". www.healio.com. Retrieved 31 May 2025.
^ Ma S, Gisselmann G, Vogt-Eisele AK, Doerner JF, Hatt H (October 2008). "Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels". Pakistan Journal of Pharmaceutical Sciences. 21 (4): 370–378. PMID 18930858.
^ Kühn FJ, Kühn C, Lückhoff A (February 2009). "Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives". The Journal of Biological Chemistry. 284 (7): 4102–4111. doi:10.1074/jbc.M806651200. PMID 19095656.
^ Bödding M, Wissenbach U, Flockerzi V (December 2007). "Characterisation of TRPM8 as a pharmacophore receptor". Cell Calcium. 42 (6): 618–28. doi:10.1016/j.ceca.2007.03.005. PMID 17517434.
^ Sherkheli MA, Vogt-Eisele AK, Bura D, Beltrán Márques LR, Gisselmann G, Hatt H (2010). "Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship". Journal of Pharmacy & Pharmaceutical Sciences. 13 (2): 242–53. doi:10.18433/j3n88n. PMID 20816009.
^ Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE (October 2013). "TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain". Pain. 154 (10): 2169–77. doi:10.1016/j.pain.2013.06.043. PMC 3778045. PMID 23820004.
^ Peixoto-Neves D, Soni H, Adebiyi A (November 2018). "Oxidant-induced increase in norepinephrine secretion from PC12 cells is dependent on TRPM8 channel-mediated intracellular calcium elevation". Biochemical and Biophysical Research Communications. 506 (3): 709–715. doi:10.1016/j.bbrc.2018.10.120. PMID 30376995. S2CID 53107273.
^ Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY (March 2019). "Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel". Science. 363 (6430). doi:10.1126/science.aav9334. PMC 6478609. PMID 30733385.
^ Wirta DL, Senchyna M, Lewis AE, Evans DG, McLaurin EB, Ousler GW, et al. (October 2022). "A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1)". The Ocular Surface. 26: 166–173. doi:10.1016/j.jtos.2022.08.003. PMID 35970431.

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[1] "Acoltremon - Alcon". AdisInsight. Springer Nature Switzerland AG.

[2] "Novel Drug Approvals for 2025". U.S. Food and Drug Administration (FDA). 29 May 2025. Retrieved 29 May 2025.

[3] "Alcon Announces FDA Approval of Tryptyr (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease" (Press release). Alcon. 28 May 2025. Retrieved 29 May 2025 – via Business Wire.

[4] "FDA approves Tryptyr to treat dry eye signs, symptoms". www.healio.com. Retrieved 31 May 2025.

[Ma_2008-5] Ma S, Gisselmann G, Vogt-Eisele AK, Doerner JF, Hatt H (October 2008). "Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels". Pakistan Journal of Pharmaceutical Sciences. 21 (4): 370–378. PMID 18930858.

[Frank_2009-6] Kühn FJ, Kühn C, Lückhoff A (February 2009). "Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives". The Journal of Biological Chemistry. 284 (7): 4102–4111. doi:10.1074/jbc.M806651200. PMID 19095656.

[7] Bödding M, Wissenbach U, Flockerzi V (December 2007). "Characterisation of TRPM8 as a pharmacophore receptor". Cell Calcium. 42 (6): 618–28. doi:10.1016/j.ceca.2007.03.005. PMID 17517434.

[8] Sherkheli MA, Vogt-Eisele AK, Bura D, Beltrán Márques LR, Gisselmann G, Hatt H (2010). "Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship". Journal of Pharmacy & Pharmaceutical Sciences. 13 (2): 242–53. doi:10.18433/j3n88n. PMID 20816009.

[9] Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE (October 2013). "TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain". Pain. 154 (10): 2169–77. doi:10.1016/j.pain.2013.06.043. PMC 3778045. PMID 23820004.

[10] Peixoto-Neves D, Soni H, Adebiyi A (November 2018). "Oxidant-induced increase in norepinephrine secretion from PC12 cells is dependent on TRPM8 channel-mediated intracellular calcium elevation". Biochemical and Biophysical Research Communications. 506 (3): 709–715. doi:10.1016/j.bbrc.2018.10.120. PMID 30376995. S2CID 53107273.

[11] Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY (March 2019). "Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel". Science. 363 (6430). doi:10.1126/science.aav9334. PMC 6478609. PMID 30733385.

[12] Wirta DL, Senchyna M, Lewis AE, Evans DG, McLaurin EB, Ousler GW, et al. (October 2022). "A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1)". The Ocular Surface. 26: 166–173. doi:10.1016/j.jtos.2022.08.003. PMID 35970431.

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