# Acoltremon

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Acoltremon
> Markdown URL: https://mediated.wiki/source/Acoltremon.md
> Source: https://en.wikipedia.org/wiki/Acoltremon
> Source revision: 1335540293
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical compound}}
{{Use dmy dates|date=May 2025}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image = Acoltremon.svg
| image_class = skin-invert-image
| width = 
| alt = 
| caption = Molecular structure of acoltremon
| image2 = Acoltremon 3D.png
| image_class2 = bg-transparent
| alt2 = 
| caption2 = 3D representation of an acoltremon molecule
| pronounce = 
| tradename = Tryptyr
| Drugs.com = {{drugs.com|monograph|acoltremon}}
| MedlinePlus = a625071
| DailyMedID = Acoltremon
| pregnancy_AU = 
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [Eye drop](/source/Ophthalmic_drug_administration)
| class = 
| ATC_prefix = None
| ATC_suffix = 
| ATC_supplemental = <!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 -->
| legal_BR_comment = 
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = <ref name="Tryptyr FDA label">{{cite web | title=Tryptyr- acoltremon solution | website=DailyMed | date=12 June 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b7715a1-035c-4002-b582-5238efee5d58 | access-date=6 July 2025}}</ref>
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->| bioavailability = 
| protein_bound = 
| metabolism = 
| metabolites = 
| onset = 
| elimination_half-life = 
| duration_of_action = 
| excretion = <!-- Identifiers -->
| CAS_number = 68489-09-8
| PubChem = 11266244
| IUPHAR_ligand = 
| DrugBank = DB19202
| ChemSpiderID = 9441255
| UNII = 1L7BVT4Z4Z
| KEGG = D13125
| ChEBI = 
| ChEMBL = 2441929
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = AVX-012, WS-12

<!-- Chemical and physical data -->| IUPAC_name = (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide
| C = 18
| H = 27
| N = 1
| O = 2
| SMILES = C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C
| StdInChI = 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
| StdInChIKey = HNSGVPAAXJJOPQ-XOKHGSTOSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
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| sol_units = 
| specific_rotation = 
}}

'''Acoltremon''' sold under the brand name '''Tryptyr''', is a [medication](/source/medication) used for the treatment of [dry eye syndrome](/source/dry_eye_syndrome).<ref name="Tryptyr FDA label" /> Acoltremon is a [transient receptor potential melastatin 8](/source/TRPM8) (TRPM8) thermoreceptor agonist.<ref name="Tryptyr FDA label" /> It is used as an [eye drop](/source/Ophthalmic_drug_administration).<ref name="Tryptyr FDA label" />

The most common treatment-emergent adverse event experienced during the clinical studies was instillation site pain (burning or stinging) events.<ref name="Tryptyr FDA snapshot">{{cite web | title=Drug Trials Snapshot: Tryptyr | website=U.S. Food and Drug Administration | date=28 May 2025 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-tryptyr | access-date=24 August 2025}} {{PD-notice}}</ref>

Acoltremon was approved for medical use in the United States in May 2025.<ref name="Tryptyr FDA snapshot" />

== Medical uses ==
Acoltremon is [indicated](/source/indicated) for the treatment of the signs and symptoms of dry eye disease.<ref name="Tryptyr FDA label" /><ref name="Tryptyr FDA snapshot" />

== Pharmacology ==
Acoltremon acts as a potent and selective activator ([opener](/source/channel_opener)) of the [TRPM8](/source/TRPM8) calcium channel, which is responsible for the sensation of coldness produced by [menthol](/source/menthol).<ref name="Ma_2008">{{cite journal | vauthors = Ma S, Gisselmann G, Vogt-Eisele AK, Doerner JF, Hatt H | title = Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels | journal = Pakistan Journal of Pharmaceutical Sciences | volume = 21 | issue = 4 | pages = 370–378 | date = October 2008 | pmid = 18930858 }}</ref> It is slightly less potent as a TRPM8 activator compared to [icilin](/source/icilin), but is a much more selective TRPM8 ligand when compared to menthol.<ref name="Frank_2009">{{cite journal | vauthors = Kühn FJ, Kühn C, Lückhoff A | title = Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives | journal = The Journal of Biological Chemistry | volume = 284 | issue = 7 | pages = 4102–4111 | date = February 2009 | pmid = 19095656 | doi = 10.1074/jbc.M806651200 | doi-access = free }}</ref>

== History ==
The US [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) approved acoltremon based on evidence from two clinical trials (COMET-2 and COMET-3) of 931 participants with dry eye disease.<ref name="Tryptyr FDA snapshot" /> The trials were conducted at 46 sites in the United States.<ref name="Tryptyr FDA snapshot" /> Two additional studies: COMET-1 and COMET-4 were included in the evaluation of safety benefit of acoltremon.<ref name="Tryptyr FDA snapshot" /> The number of participants representing efficacy findings may differ from the number of participants representing safety findings due to different pools of study participants analyzed for efficacy and safety.<ref name="Tryptyr FDA snapshot" /> Both COMET-2 and COMET-3 are phase III, multi-center, vehicle-controlled, double-masked, randomized studies whose primary endpoint was proportion of participants with ≥10 mm increase from baseline in unanesthetized Schirmer Score on day 14.<ref name="Tryptyr FDA snapshot" /> COMET-1 was a phase IIb multi-center, vehicle-controlled, double-masked, randomized study conducted at 15 sites in the United States which randomized 369 participants with a history of dry eye disease.<ref name="Tryptyr FDA snapshot" /> COMET-4 was a multi-center, vehicle-controlled, double-masked, randomized study conducted at approximately 10 sites in the United States which enrolled 275 participants with a history of dry eye disease.<ref name="Tryptyr FDA snapshot" /> Study COMET-2 and COMET-3 have a similar design.<ref name="Tryptyr FDA snapshot" /> Each study is a multi-center, randomized, double-masked, vehicle-controlled phase III study.<ref name="Tryptyr FDA snapshot" /> The primary objective of these studies was to evaluate the safety and efficacy of acoltremon compared to vehicle.<ref name="Tryptyr FDA snapshot" /> Participants 30 years and older with a history of artificial tear use for dry eye disease were qualified based on signs and symptoms of dry eye disease at screening, and were requalified at baseline (day 1) following a 14-day vehicle run-in.<ref name="Tryptyr FDA snapshot" /> COMET 2 enrolled 465 participants at 23 study sites, whereas COMET-3 enrolled 466 participants at 23 sites.<ref name="Tryptyr FDA snapshot" />

== Society and culture ==
=== Legal status ===
Acoltremon was approved for medical use in the United States in May 2025.<ref>{{cite press release | title=Alcon Announces FDA Approval of Tryptyr (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease | publisher=Alcon | via=Business Wire | date=28 May 2025 | url=https://www.businesswire.com/news/home/20250526316115/en/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0.003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease | access-date=29 May 2025 | archive-date=29 May 2025 | archive-url=https://web.archive.org/web/20250529233003/https://www.businesswire.com/news/home/20250526316115/en/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0.003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease | url-status=live }}</ref>

=== Names ===
Acoltremon is the [international nonproprietary name](/source/international_nonproprietary_name).<ref>{{cite journal | year = 2023 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 89 | journal = WHO Drug Information | volume = 37 | issue = 1 | hdl = 10665/366661 | hdl-access = free}}</ref>

Acoltremon is sold under the brand name Tryptyr.<ref name="Tryptyr FDA snapshot" />

== References ==
{{Reflist}}

== External links ==
* {{ClinicalTrialsGov|NCT05285644|Study Evaluating the Safety and Efficacy of AR-15512 (COMET-2)}}
* {{ClinicalTrialsGov|NCT05360966|Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3)}}

{{Transient receptor potential channel modulators}}
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Category:Ophthalmology drugs
Category:Ion channel openers
Category:Amides
Category:Cooling flavors

{{Pharma-stub}}

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Adapted from the Wikipedia article [Acoltremon](https://en.wikipedia.org/wiki/Acoltremon) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Acoltremon?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.