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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-08-12 19:15:31 UTC
Update Date2019-07-23 05:45:45 UTC
HMDB IDHMDB0003352
Secondary Accession Numbers
  • HMDB03352
Metabolite Identification
Common NameMenthol
DescriptionMenthol is an alcohol produced from mint oils or prepared synthetically. Menthol is a covalent organic compound made synthetically or obtained from peppermint or other mint oils. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is (-)-menthol, which is assigned the (1R,2S,5R) configuration. Menthol has local anesthetic and counterirritant qualities, and it is widely used to relieve minor throat irritation.
Structure
Data?1563860745
Synonyms
ValueSource
(-)-(1R,3R,4S)-MentholChEBI
(1alpha,2beta,5alpha)-5-Methyl-2(1-methylethyl)cyclohexanolChEBI
(1R,3R,4S)-(-)-MentholChEBI
(1R-(1-alpha,2-beta,5-alpha))-5-Methyl-2-(1-methylethyl)cyclohexanolChEBI
L-MentholChEBI
LevomentholChEBI
LevomentholumChEBI
LevomentolChEBI
(1a,2b,5a)-5-Methyl-2(1-methylethyl)cyclohexanolGenerator
(1Α,2β,5α)-5-methyl-2(1-methylethyl)cyclohexanolGenerator
(1R-(1-a,2-b,5-a))-5-Methyl-2-(1-methylethyl)cyclohexanolGenerator
(1R-(1-Α,2-β,5-α))-5-methyl-2-(1-methylethyl)cyclohexanolGenerator
(-)-Menthyl alcoholHMDB
(-)-trans-p-Menthan-cis-olHMDB
(1R)-(-)-MentholHMDB
(1R,2S,5R)-(-)-MentholHMDB
(R)-(-)-MentholHMDB
1-MentholHMDB
2-Isopropyl-5-methylcyclohexanolHMDB
5-Methyl-2-(1-methylethyl)cyclohexanolHMDB
5-Methyl-2-propan-2-ylcyclohexan-1-olHMDB
D-(-)-MentholHMDB
HexahydrothymolHMDB
L-(-)-MentholHMDB
MenthacamphorHMDB
MenthomentholHMDB
p-Menthan-3-olHMDB
Peppermint camphorHMDB
U.S.p. mentholHMDB
KerasalHMDB
Menthol, (1alpha,2beta,5alpha)-isomerHMDB
MentholMeSH
Chemical FormulaC10H20O
Average Molecular Weight156.269
Monoisotopic Molecular Weight156.151415264
IUPAC Name(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol
Traditional Namementhol
CAS Registry Number2216-51-5
SMILES
CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O
InChI Identifier
InChI=1S/C10H20O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-11H,4-6H2,1-3H3/t8-,9+,10-/m1/s1
InChI KeyNOOLISFMXDJSKH-KXUCPTDWSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as menthane monoterpenoids. These are monoterpenoids with a structure based on the o-, m-, or p-menthane backbone. P-menthane consists of the cyclohexane ring with a methyl group and a (2-methyl)-propyl group at the 1 and 4 ring position, respectively. The o- and m- menthanes are much rarer, and presumably arise by alkyl migration of p-menthanes.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassMonoterpenoids
Direct ParentMenthane monoterpenoids
Alternative Parents
Substituents
  • P-menthane monoterpenoid
  • Monocyclic monoterpenoid
  • Cyclohexanol
  • Cyclic alcohol
  • Secondary alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point43 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.49 mg/mL at 25 °CNot Available
LogP3.40GRIFFIN,S ET AL. (1999)
Predicted Properties
PropertyValueSource
Water Solubility0.56 g/LALOGPS
logP2.68ALOGPS
logP2.66ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)19.55ChemAxon
pKa (Strongest Basic)-0.81ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity47.45 m³·mol⁻¹ChemAxon
Polarizability19.69 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-0006-1900000000-cc06fe70d7649d059f92JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00ea-9100000000-0be605183591bf5f33a0JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00ea-9100000000-977cf0c036d597693bebJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0006-1900000000-cc06fe70d7649d059f92JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-9600000000-fcf4b2a96455b111f889JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-01w0-9520000000-26cc8cab97979ec9fb4dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-053r-9300000000-d9c35833e73c8655fb23JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0ldl-9000000000-abf2f837df49fbedc53cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0007-9000000000-adee6385265c6606326dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-D-3000) , Positivesplash10-00ea-9100000000-e3f1b7b69a021063fabbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-DX-300) , Positivesplash10-00ea-9100000000-d69777874c9615b7e751JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052r-0900000000-39d327015211bdc2b4e8JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052r-6900000000-67e6c41c2a8d759d6cafJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0aor-9200000000-88888989ba15a9dc0269JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-3a700dc611fb070e6b45JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-86ed17c709dc4636ad41JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0bti-6900000000-fc116bf41f068d3f6f75JSpectraViewer | MoNA
MSMass Spectrum (Electron Ionization)splash10-00ea-9100000000-602436010653202a4da9JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Feces
  • Saliva
  • Urine
Tissue Locations
  • Bladder
  • Mouth
  • Nerve Cells
  • Neuron
  • Skeletal Muscle
  • Stratum Corneum
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.064 (0.033 - 0.159) uMAdult (>18 years old)BothNormal details
FecesDetected but not Quantified Adult (>18 years old)BothNormal details
FecesDetected but not Quantified Children (1-13 years old)BothNormal details
FecesDetected but not Quantified Adult (>18 years old)Female
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
SalivaDetected but not Quantified Children (1-13 years old)BothNormal details
SalivaDetected but not Quantified Adult (>18 years old)Not SpecifiedNormal details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected but not Quantified Adult (>18 years old)BothNormal details
UrineDetected but not Quantified Adult (>18 years old)BothNormal
    • Zhang, S., Liu, L...
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
FecesDetected but not Quantified Adult (>18 years old)BothImmunoglobulin A nephropathy (IgAN) non progressor details
FecesDetected but not Quantified Adult (>18 years old)BothImmunoglobulin A nephropathy (IgAN) progressor details
FecesDetected but not Quantified Children (1-13 years old)BothPervasive Developmental Disorder Not Otherwise Specified details
FecesDetected but not Quantified Adult (>18 years old)Female
Nonalcoholic fatty liver disease
details
SalivaDetected but not Quantified Children (1-13 years old)BothCeliac disease details
UrineDetected but not Quantified Adult (>18 years old)BothBreast cancer details
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease References
Nonalcoholic fatty liver disease
  1. Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers RP, Rioux KP: Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2013 Jul;11(7):868-75.e1-3. doi: 10.1016/j.cgh.2013.02.015. Epub 2013 Feb 27. [PubMed:23454028 ]
Pervasive developmental disorder not otherwise specified
  1. De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R: Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One. 2013 Oct 9;8(10):e76993. doi: 10.1371/journal.pone.0076993. eCollection 2013. [PubMed:24130822 ]
Celiac disease
  1. Francavilla R, Ercolini D, Piccolo M, Vannini L, Siragusa S, De Filippis F, De Pasquale I, Di Cagno R, Di Toma M, Gozzi G, Serrazanetti DI, De Angelis M, Gobbetti M: Salivary microbiota and metabolome associated with celiac disease. Appl Environ Microbiol. 2014 Jun;80(11):3416-25. doi: 10.1128/AEM.00362-14. Epub 2014 Mar 21. [PubMed:24657864 ]
Perillyl alcohol administration for cancer treatment
  1. Silva CL, Passos M, Camara JS: Solid phase microextraction, mass spectrometry and metabolomic approaches for detection of potential urinary cancer biomarkers--a powerful strategy for breast cancer diagnosis. Talanta. 2012 Jan 30;89:360-8. doi: 10.1016/j.talanta.2011.12.041. Epub 2011 Dec 22. [PubMed:22284503 ]
Associated OMIM IDs
DrugBank IDDB00825
Phenol Explorer Compound IDNot Available
FoodDB IDFDB014499
KNApSAcK IDC00000810
Chemspider ID15803
KEGG Compound IDC00400
BioCyc ID--MENTHOL
BiGG IDNot Available
Wikipedia LinkMenthol
METLIN IDNot Available
PubChem Compound16666
PDB IDNot Available
ChEBI ID15409
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceBergner, Eike Johannes; Ebel, Klaus; Johann, Thorsten; Loeber, Oliver. Method for the production of menthol. PCT Int. Appl. (2006), 32 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Stich HF, Stich W: Chromosome-damaging activity of saliva of betel nut and tobacco chewers. Cancer Lett. 1982 Mar-Apr;15(3):193-202. [PubMed:7116324 ]
  2. Haahr AM, Bardow A, Thomsen CE, Jensen SB, Nauntofte B, Bakke M, Adler-Nissen J, Bredie WL: Release of peppermint flavour compounds from chewing gum: effect of oral functions. Physiol Behav. 2004 Sep 15;82(2-3):531-40. [PubMed:15276819 ]
  3. Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P: Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol. 2006 Mar 6;6:6. [PubMed:16519806 ]
  4. Rohacs T, Lopes CM, Michailidis I, Logothetis DE: PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci. 2005 May;8(5):626-34. Epub 2005 Apr 24. [PubMed:15852009 ]
  5. Valdez JS, Martin DK, Mayersohn M: Sensitive and selective gas chromatographic methods for the quantitation of camphor, menthol and methyl salicylate from human plasma. J Chromatogr B Biomed Sci Appl. 1999 Jun 11;729(1-2):163-71. [PubMed:10410939 ]
  6. Eccles R: Menthol and related cooling compounds. J Pharm Pharmacol. 1994 Aug;46(8):618-30. [PubMed:7529306 ]
  7. Haeseler G, Maue D, Grosskreutz J, Bufler J, Nentwig B, Piepenbrock S, Dengler R, Leuwer M: Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol. Eur J Anaesthesiol. 2002 Aug;19(8):571-9. [PubMed:12200946 ]
  8. Gelal A, Jacob P 3rd, Yu L, Benowitz NL: Disposition kinetics and effects of menthol. Clin Pharmacol Ther. 1999 Aug;66(2):128-35. [PubMed:10460066 ]
  9. Grigoleit HG, Grigoleit P: Pharmacology and preclinical pharmacokinetics of peppermint oil. Phytomedicine. 2005 Aug;12(8):612-6. [PubMed:16121523 ]
  10. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A: ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003 Mar 21;112(6):819-29. [PubMed:12654248 ]
  11. Xu H, Blair NT, Clapham DE: Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J Neurosci. 2005 Sep 28;25(39):8924-37. [PubMed:16192383 ]
  12. Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N, Chancellor MB, De Miguel F: Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol. 2004 Sep;172(3):1175-8. [PubMed:15311065 ]
  13. Narishetty ST, Panchagnula R: Effect of L-menthol and 1,8-cineole on phase behavior and molecular organization of SC lipids and skin permeation of zidovudine. J Control Release. 2005 Jan 20;102(1):59-70. [PubMed:15653134 ]
  14. Prescott J: The generalizability of capsaicin sensitization and desensitization. Physiol Behav. 1999 Jul;66(5):741-9. [PubMed:10405101 ]
  15. Liu Y, Ye X, Feng X, Zhou G, Rong Z, Fang C, Chen H: Menthol facilitates the skin analgesic effect of tetracaine gel. Int J Pharm. 2005 Nov 23;305(1-2):31-6. Epub 2005 Oct 10. [PubMed:16219435 ]

Enzymes

General function:
Involved in ion channel activity
Specific function:
Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonists menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing
Gene Name:
TRPM8
Uniprot ID:
Q7Z2W7
Molecular weight:
127684.0
References
  1. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A: ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003 Mar 21;112(6):819-29. [PubMed:12654248 ]
  2. Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R: Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol. 2004 Feb;141(4):737-45. Epub 2004 Feb 2. [PubMed:14757700 ]
  3. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A: Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004 Mar 25;41(6):849-57. [PubMed:15046718 ]
  4. Andersson DA, Chase HW, Bevan S: TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH. J Neurosci. 2004 Jun 9;24(23):5364-9. [PubMed:15190109 ]
  5. Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N, Chancellor MB, De Miguel F: Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol. 2004 Sep;172(3):1175-8. [PubMed:15311065 ]
  6. Eccles R: Menthol and related cooling compounds. J Pharm Pharmacol. 1994 Aug;46(8):618-30. [PubMed:7529306 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular weight:
42644.7
References
  1. Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C: Menthol: a natural analgesic compound. Neurosci Lett. 2002 Apr 12;322(3):145-8. [PubMed:11897159 ]
  2. Taniguchi Y, Deguchi Y, Saita M, Noda K: [Antinociceptive effects of counterirritants]. Nihon Yakurigaku Zasshi. 1994 Dec;104(6):433-46. [PubMed:7851817 ]
General function:
Involved in calcium channel activity
Specific function:
Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity
Gene Name:
TRPV3
Uniprot ID:
Q8NET8
Molecular weight:
90635.1
References
  1. Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapoutian A, Story GM: More than cool: promiscuous relationships of menthol and other sensory compounds. Mol Cell Neurosci. 2006 Aug;32(4):335-43. Epub 2006 Jul 7. [PubMed:16829128 ]
General function:
Not Available
Specific function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)- tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular weight:
127485.8
References
  1. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A: ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003 Mar 21;112(6):819-29. [PubMed:12654248 ]
  2. Namer B, Seifert F, Handwerker HO, Maihofner C: TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport. 2005 Jun 21;16(9):955-9. [PubMed:15931068 ]
  3. Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapoutian A, Story GM: More than cool: promiscuous relationships of menthol and other sensory compounds. Mol Cell Neurosci. 2006 Aug;32(4):335-43. Epub 2006 Jul 7. [PubMed:16829128 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]