Levomenthol

Summary

Levomenthol (CHEMBL470670) is a phase-3 clinical-stage small-molecule antipruritic drug targeting TRPA1, TRPM8, and TRPV3; indicated across 1 condition including chronic obstructive pulmonary disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (TRPA1, TRPM8, TRPV3)
• Indications: 1 condition
• Clinical trials: 41
• Chemistry: 156.26 Da · C10H20O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL470670
Name	Levomenthol
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	16666
ChEBI	CHEBI:15409
Molecular formula	C10H20O
Molecular weight	156.26
InChIKey	NOOLISFMXDJSKH-KXUCPTDWSA-N

SMILES: C[C@@H]1CC[C@H]([C@@H](C1)O)C(C)C

IUPAC name: (1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexan-1-ol

ChEBI definition: A p-menthan-3-ol which has (1R,2S,5R)-stereochemistry. It is the most common naturally occurring enantiomer.

Pharmacological roles (ChEBI): antipruritic drug, antitussive, antispasmodic drug.

Also known as: L-menthol, Levomenthol, Levomentol, (-)-menthol, l-menthol, (-) Menthol, L-Menthol, SID144213316, SID144209021, SID144213345, SID144205173, SID144209117

Patent coverage: 64,645 distinct patent families (182,553 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TRPA1	TRPA1	Partial agonist	4.5	0.1%	O75762
TRPM8	TRPM8		4.6	0.5%	Q7Z2W7
TRPV3	TRPV3	Activation	1.7	0%	Q8NET8

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Transient receptor potential cation channel subfamily M member 8, Voltage-dependent L-type calcium channel subunit alpha-1C, Transient receptor potential cation channel subfamily A member 1.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TRPM8	5.42	EC50	3800	nM	CHEMBL_ACT_28755500
TRPM8	5	EC50	10100	nM	CHEMBL_ACT_18269243

Target pathways

Aggregated over 3 target gene(s): TRPA1, TRPM8, TRPV3.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
TRP channels	3	TRPA1, TRPM8, TRPV3

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	3
calcium ion transmembrane transport	3
calcium ion transport	3
monoatomic ion transmembrane transport	3
transmembrane transport	3
intracellular calcium ion homeostasis	2
response to cold	2
thermoception	2
calcium-mediated signaling	2
response to temperature stimulus	2
cell surface receptor signaling pathway	1
response to xenobiotic stimulus	1
urinary bladder smooth muscle contraction	1
sensory perception of pain	1
cellular response to heat	1

Indications & clinical

Indications

1 indication (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
chronic obstructive pulmonary disease	2	MONDO:0005002	EFO:0000341

Clinical trials

Total trials: 41.

Phase distribution

Phase	Trials
Not specified	19
PHASE2	8
PHASE1	6
PHASE3	3
EARLY_PHASE1	2
PHASE4	1
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02984072	PHASE4	COMPLETED	Menthol for PDT Pain Relief
NCT01408446	PHASE2/PHASE3	COMPLETED	Effects and Safety of Menthol on Blood Pressure and Metabolic Parameters in Prehypertensive and Mild Hypertensive Patients
NCT01411176	PHASE3	COMPLETED	Phase III Study of NPO-11 in Patients Undergoing Therapeutic Upper Gastrointestinal Endoscopy
NCT01411189	PHASE3	COMPLETED	Phase III Open-labeled Study of NPO-11 in Patients Undergoing Therapeutic Upper Gastrointestinal Endoscopy
NCT04593836	PHASE3	UNKNOWN	Antiperistaltic Effect and Safety of L-menthol in the Elderly With Contraindication to Buscopan
NCT07398287	PHASE2	RECRUITING	Efficacy of L-menthol on Breathlessness in Interstitial Lung Disease
NCT07500974	PHASE2	NOT_YET_RECRUITING	Efficacy of L-menthol on Breathlessness in Asthma
NCT01855607	PHASE2	TERMINATED	Topical Menthol for the Treatment of Chemotherapy Induced Peripheral Neuropathy
NCT02728687	PHASE1/PHASE2	COMPLETED	Topical Menthol +/- Mannitol for Painful Diabetic Peripheral Neuropathy
NCT03050957	PHASE2	COMPLETED	Effect of Oral Menthol on the Swallow Response of Patients With Oropharyngeal Dysphagia Associated With Neurological Diseases and Aging
NCT04097574	PHASE2	COMPLETED	Study of NPO-13 During Colonoscopy
NCT04484428	PHASE2	TERMINATED	A Study to Evaluate the Efficacy and Safety of K-285 Compared With Menthol Gel for the Treatment of Delayed Onset Muscle Soreness (DOMS) in the Lower Extremity
NCT05877079	PHASE2	COMPLETED	TRPM8 in Acute Ischemic Stroke by Topical Menthol
NCT05888597	PHASE2	COMPLETED	Efficacy of L-menthol on Breathlessness in Chronic Obstructive Pulmonary Disease
NCT02169154	PHASE1	COMPLETED	A Safety Study to Investigate the Skin Irritancy Potential of Diclofenac-Menthol Gel
NCT02201238	PHASE1	COMPLETED	Pharmacokinetics Study Comparing Topical Diclofenac/Menthol Gels With Voltaren Gel and Oral Diclofenac Sodium
NCT02666846	PHASE1	COMPLETED	Assess the Efficacy and Safety in Volunteers of DCF100, TIB200 and SPR300 vs. Placebo and Control(s) in a UV Pain Model
NCT03168191	PHASE1	COMPLETED	Flavors and E-cigarette Effects in Adolescent Smokers- STUDY 2
NCT04900129	PHASE1	COMPLETED	Inhalation of Vapor With Medication (Diclofenac Sodium, Menthol, Methyl Salicylate and N-Acetyl Cysteine) Reduces Oxygen Need and Hospital Stay in COVID-19 Patients - A Case Control Study
NCT05106400	PHASE1	COMPLETED	Clinical Adhesion Study Between ZTlido 1.8% and Three Over-the-counter External Analgesic Lidocaine-containing Patches
NCT03243630	EARLY_PHASE1	COMPLETED	Effects of Flavors on Nicotine Reinforcement in Smokers
NCT06811051	EARLY_PHASE1	UNKNOWN	Effect of Clove Oil and Menthol Lozenges on Post-extubation Sore Throat
NCT05785026	Not specified	RECRUITING	Menthol for Dyspnea Relief in Health and COPD
NCT05896033	Not specified	RECRUITING	Impact of Cigarette and E-cigarette Menthol Regulation on Current Smokers of Menthol Cigarettes
NCT06857760	Not specified	RECRUITING	Effects of Three Different Methods Applied to Patients After Spine Surgery on Nausea, Thirst and Comfort
NCT07508371	Not specified	NOT_YET_RECRUITING	Menthol Massage for Post-Bypass Pain & Anxiety
NCT00743990	Not specified	COMPLETED	Effect of Effect of a Medicated Topical Therapy , Petrolatum, and No Treatment on Nocturnal Cough
NCT01716767	Not specified	COMPLETED	Acute Effect of Topical Menthol on Carpal Tunnel Syndrome
NCT02102100	Not specified	COMPLETED	The Effects of Menthol as Delivered by an Electronic Cigarette on the Desirability of Nicotine in Tobacco Users
NCT02403687	Not specified	COMPLETED	Prospective Analgesic Compound Efficacy (PACE) Study
NCT02653703	Not specified	COMPLETED	L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain
NCT03132142	Not specified	UNKNOWN	Desensitization of Nociceptive Afferents by Application of Topical Capsaicin, Trans-cinnamaldehyde and L-menthol
NCT03236623	Not specified	UNKNOWN	Menthol Popsicle to Manage the Patient’s Seat in the Preoperative Period.
NCT03621800	Not specified	COMPLETED	Menthol Popsicle to Manage the Elderly Patient’s Thirst in the Immediate Postoperative Period
NCT03943407	Not specified	WITHDRAWN	Characterization of the Toll-like Receptor 7-agonist Imiquimod 3.75% As a New Surrogate Model of Itch
NCT04711044	Not specified	COMPLETED	Investigation of a New Human Model for Itch
NCT04879225	Not specified	COMPLETED	Menthol and Mint Experimental Tobacco Marketplace (ETM) Study
NCT04994262	Not specified	COMPLETED	The Effect on Thirst, Nausea-Vomiting and Comfort Levels of Menthol Lozenge Applied After Extubation
NCT05429814	Not specified	COMPLETED	Topical Menthol Application in Chemotherapy-Related Peripheral Neuropathy in Patients With Breast Cancer
NCT05632692	Not specified	UNKNOWN	Menthol Mouth Rinsing and Performance Responses of Elite Football Referees in the Heat

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

35 molecules share ≥1 primary target. Top 35 by shared-target count:

Molecule	Source	Status	Shared targets
CANNABIDIVARIN	ChEMBL	Phase 2	TRPA1, TRPM8, TRPV3
CANNABIGEROL	ChEMBL	Phase 2	TRPA1, TRPM8, TRPV3
TETRAHYDROCANNABIVARIN	ChEMBL	Phase 2	TRPA1, TRPM8, TRPV3
dronabinol	ChEMBL + PubChem	Phase 4 (approved)	TRPA1, TRPM8
MENTHOL	ChEMBL	Phase 4 (approved)	TRPA1, TRPM8
CANNABINOL	ChEMBL	Phase 3	TRPA1, TRPV3
ICILLIN	ChEMBL	Phase 3	TRPA1, TRPM8
camphor (synthetic)	PubChem	Approved	TRPA1, TRPV3
Eugenol	PubChem	Approved	TRPA1, TRPM8
menthol, unspecified form	PubChem	Approved	TRPA1, TRPM8
CANNABIDIOL	ChEMBL + PubChem	Phase 4 (approved)	TRPM8
CAPSAICIN	ChEMBL + PubChem	Phase 4 (approved)	TRPM8
CLOTRIMAZOLE	ChEMBL + PubChem	Phase 4 (approved)	TRPM8
DICLOFENAC	ChEMBL + PubChem	Phase 4 (approved)	TRPA1
DISULFIRAM	ChEMBL + PubChem	Phase 4 (approved)	TRPA1
ECONAZOLE	ChEMBL + PubChem	Phase 4 (approved)	TRPM8
MEFENAMIC ACID	ChEMBL + PubChem	Phase 4 (approved)	TRPA1
NICOTINE	ChEMBL	Phase 4 (approved)	TRPA1
RESVERATROL	ChEMBL + PubChem	Phase 3 (approved)	TRPA1
ACOLTREMON	ChEMBL	Phase 2	TRPM8
ALLICIN	ChEMBL	Phase 2	TRPA1
CARVACROL	ChEMBL	Phase 2	TRPA1
CHLORDANTOIN	ChEMBL	Phase 2	TRPA1
ELISMETREP	ChEMBL	Phase 2	TRPM8
FLUFENAMIC ACID	ChEMBL	Phase 2	TRPA1
RG6341	ChEMBL	Phase 2	TRPA1
SALIRASIB	ChEMBL	Phase 2	TRPA1
SANGUINARIUM	ChEMBL	Phase 2	TRPA1
SB-705498	ChEMBL	Phase 2	TRPM8
THYMOL	ChEMBL	Phase 2	TRPA1
Acetaldehyde	PubChem	Approved	TRPA1
Caffeine	PubChem	Approved	TRPA1
eucalyptol	PubChem	Approved	TRPM8
Propylene Glycol	PubChem	Approved	TRPA1
Serotonin	PubChem	Approved	TRPM8