DT-Web

DB00825 - Menthol


Identification
Name Menthol
Accession Number DB00825 (APRD01604)
Type small molecule
Description 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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 156.2652
Groups approved
Monoisotopic Weight 156.151415262
Pharmacology
Indication Used to treat occasional minor irritation, pain, sore mouth, and sore throat as well as cough associated with a cold or inhaled irritants.
Mechanism of action Menthol primarily activates the cold-sensitive TRPM8 receptors in the skin. Menthol, after topical application, causes a feeling of coolness due to stimulation of 'cold' receptors by inhibiting Ca++ currents of neuronal membranes. It may also yield analgesic properties via kappa-opioid receptor agonism.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Menthol, DL: ORAL (LD50): Acute: 2900 mg/kg [Rat], 3100 mg/kg [Mouse]. DERMAL (LD50): Acute: 5001 mg/kg [Rabbit].
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Transient receptor potential cation channel subfamily M member 8
Name Transient receptor potential cation channel subfamily M member 8
Gene Name TRPM8
Pharmacological action yes
Actions inducer
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • Eccles R: Menthol and related cooling compounds. J Pharm Pharmacol. 1994 Aug;46(8):618-30. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3683
Transient receptor potential cation channel subfamily A member 1
Name Transient receptor potential cation channel subfamily A member 1
Gene Name TRPA1
Pharmacological action yes
Actions inducer
References
  • 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
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3684
Transient receptor potential cation channel subfamily V member 3
Name Transient receptor potential cation channel subfamily V member 3
Gene Name TRPV3
Pharmacological action yes
Actions inducer
References
  • 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
DTHybrid score 1.3684
Kappa-type opioid receptor
Name Kappa-type opioid receptor
Gene Name OPRK1
Pharmacological action unknown
Actions agonist
References
  • 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
  • Taniguchi Y, Deguchi Y, Saita M, Noda K: [Antinociceptive effects of counterirritants] Nippon Yakurigaku Zasshi. 1994 Dec;104(6):433-46. - Pubmed
DTHybrid score 0.7493

Predictions


Id Partner name Gene Name Score
847 Mu-type opioid receptor OPRM1 0.2465
467 Delta-type opioid receptor OPRD1 0.2132
1716 Tripartite motif-containing protein 13 TRIM13 0.0402
4119 Cytochrome P450 2D6 CYP2D6 0.0323
4512 Cytochrome P450 3A4 CYP3A4 0.0299
1262 Corticotropin-lipotropin POMC 0.029
174 Sigma 1-type opioid receptor SIGMAR1 0.0184
6107 Cytochrome P450 3A7 CYP3A7 0.0153
1588 Multidrug resistance protein 1 ABCB1 0.015
4924 Cytochrome P450 2C8 CYP2C8 0.0141
4137 Nociceptin receptor OPRL1 0.0136
4118 Cytochrome P450 3A5 CYP3A5 0.012
319 Opioid receptor, sigma 1 OPRS1 0.012
4757 Cytochrome P450 2C9 CYP2C9 0.0119
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0102
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0101
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0097
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0087
6030 Cytochrome P450 2B6 CYP2B6 0.0077
341 5-hydroxytryptamine 3 receptor HTR3A 0.0071
824 Sodium-dependent serotonin transporter SLC6A4 0.0069
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0068
6016 Cytochrome P450 2C19 CYP2C19 0.0064
590 5-hydroxytryptamine 2C receptor HTR2C 0.006
1291 cAMP response element-binding protein CREB1 0.0058
587 Serum albumin ALB 0.0054
4210 Toll-like receptor 4 TLR4 0.0052
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0047
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0045
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0045
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0044
4200 Cytochrome P450 1A2 CYP1A2 0.0043
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0041
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0041
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0039
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0039
318 Alpha-2A adrenergic receptor ADRA2A 0.0038
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0038
502 5-hydroxytryptamine 2A receptor HTR2A 0.0037
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0036
492 Histamine H1 receptor HRH1 0.0035
20 Prostaglandin G/H synthase 1 PTGS1 0.0035
465 Calmodulin CALM1 0.0034
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0033
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0031
6145 Solute carrier family 22 member 1 SLC22A1 0.0029
136 Estrogen receptor ESR1 0.0029
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0028
6106 Cytochrome P450 2C18 CYP2C18 0.0023
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0022
5718 Cytochrome P450 2A6 CYP2A6 0.0018
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0018
1618 High affinity nerve growth factor receptor NTRK1 0.0017
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0016
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0016
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0016
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0013
789 Alpha-1D adrenergic receptor ADRA1D 0.0011
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0011
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0011
320 5-hydroxytryptamine 1A receptor HTR1A 0.001
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0009
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0009
556 Alpha-1A adrenergic receptor ADRA1A 0.0009
6013 Cytochrome P450 2E1 CYP2E1 0.0008
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