Identification

Name
(S)-camphor
Accession Number
DB11345
Type
Small Molecule
Groups
Experimental
Description

(S)-camphor, or L(-)-Camphor, is a stereoisomer of Camphor, a bicyclic monoterpene known to potentiate both heat and cold sensations [2]. (S)-camphor is not the naturally-occurring stereoisomer but displays similar TRPV channel affinity and current inhibition [1]. Camphor is isolated from the wood of the camphor laurel tree, Cinnamomum camphora, and had a long history of medicinal use. It has been used as a nasal decongestant and cough suppressant, and has been topically applied due to its antipruritic, analgesic, and counterirritant properties [1]. Camphor is a major active ingredient in over-the-counter balms and liniments supplied as topical analgesics by causing sensitization to heat and coolness to relieve minor muscle and joint pain [1].

Structure
Thumb
Synonyms
  • (−)-bornan-2-one
  • (−)-camphor
  • (1S,4S)-camphor
  • (1S)-(−)-camphor
  • l-camphor
External IDs
NSC-26351
Active Moieties
NameKindUNIICASInChI Key
CamphorunknownN20HL7Q941464-49-3DSSYKIVIOFKYAU-XCBNKYQSSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Balsang Pain Relief(S)-camphor (1.5 mg/100mL) + (+)-menthol (1.5 mg/100mL) + Methyl salicylate (5 mg/100mL)SolutionTopicalGenuine Drugs2015-04-20Not applicableUs
Doloran(S)-camphor (0.08 g/1g) + Menthol (0.08 g/1g) + Methyl salicylate (0.02 g/1g)OintmentTopicalHector Rivera Garzon Y Compania. S. En C.2016-10-24Not applicableUs
Doloran(S)-camphor (0.4 g/1g) + Menthol (0.1 g/1g) + Methyl salicylate (0.4 g/1g)OintmentTopicalHector Rivera Garzon Y Compania. S. En C.2016-10-242016-09-30Us
PainZone(S)-camphor (30 mg/1g) + Menthol (120 mg/1g) + Methyl salicylate (200 mg/1g)CreamTopicalMedzone Products Llc2016-07-01Not applicableUs
U Ice Cold(S)-camphor (0.5 g/100g) + Menthol (1 g/100g)OintmentTopicalUniversal Distribution Center LLC2018-08-01Not applicableUs
U Ice Cold(S)-camphor (0.5 g/100g) + Menthol (1 g/100g)OintmentTopicalNingbo Liyuan Daily Chemical Products Co., Ltd.2018-08-01Not applicableUs
Categories
Not Available
UNII
213N3S8275
CAS number
464-48-2
Weight
Average: 152.2334
Monoisotopic: 152.120115134
Chemical Formula
C10H16O
InChI Key
DSSYKIVIOFKYAU-OIBJUYFYSA-N
InChI
InChI=1S/C10H16O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7H,4-6H2,1-3H3/t7-,10+/m0/s1
IUPAC Name
(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one
SMILES
CC1(C)[C@H]2CC[C@]1(C)C(=O)C2

Pharmacology

Indication

Indicated for the temporary symptomatic relief of minor aches and pains of muscles and joints in topical analgesics.

Associated Conditions
Pharmacodynamics

Camphor exerts an analgesic action when applied topically by producing a warm sensation. It excites and desensitizes sensory nerves by activating heat-sensitive TRP vanilloid subtype 1 (TRPV1) and TRPV3 receptors. (S)-camphor is reported to exert a weaker action on TRPV1 channels, which is thought to be a result of tachyphylaxis, which is the reduction of the response to multiple stimulations [1].

Mechanism of action

TRPV3 cation channels are molecular sensors that play a role in nociception and thermosensation by inducing thermal sensation and heat-induced hyperalgesia [3]. Camphor interacts with TRPV3 channels via pore-region cysteine residues [3], leading to channel activation and a rise in intracellular calcium levels. Camphor also activates TRPV1 and a TRPV1-like current in dorsal root ganglion (DRG) neurons but inhibits the ankyrin-repeat TRP 1 (TRPA1) channel expressed in most nociceptive DRG neurons, which is responsible for the detection of temperature [1]. The precise role of TRPA1 current inhibition on the analgesic properties of camphor is unclear. Repeated stimulation by camphor leads to sensitization of the TRPV1 and TRPV3 channels, resulting in desensitization, or reduced channel response that likely leads to the analgesic effects of camphor [1]. Camphor also activates cold-sensitive transient receptor potential melastatin 8 (TRPM8) and sensitizes cold-induced calcium transients, which explains the cooling effect of camphor following dermal application. Additionally, camphor was shown to inhibit the TRPM8 receptor response to menthol [2].

TargetActionsOrganism
ATransient receptor potential cation channel subfamily V member 1
agonist
activator
Human
ATransient receptor potential cation channel subfamily V member 3
agonist
activator
Human
ATransient receptor potential cation channel subfamily A member 1
inhibitor
Human
ATransient receptor potential cation channel subfamily M member 8
activator
Human
Absorption

Absorption of camphor in the mucous membranes and the gastrointestinal tract is rapid, and peak concentration following oral ingestion occurs within 5 to 90 minutes [5].

Volume of distribution

Volume of distribution of camphor is 2 to 4 L/kg [5]. Camphor and its metabolites are relatively fat-soluble thus may accumulate in adipose and other tissues [5]. Camphor ingested by mothers was present in amnionic fluid, cord and fetal blood and fetal brain, liver and kidneys [5].

Protein binding

No pharmacokinetic data available.

Metabolism

( )-camphor undergoes rapid oxidation to 5-exo-hydroxyfenchone, which is predominantly mediated by human liver microsomal cytochrome (P450). CYP2A6 is the major enzyme involved in the hydroxylation of (-)-camphor by human liver microsomes [4].

Route of elimination

Camphor undergoes renal excretion [5].

Half life

Following oral ingestion of 200 mg camphor, the half life was 167 minutes [5].

Clearance

No pharmacokinetic data available.

Toxicity

Oral LD50 and intraperitoneal LD50 in mouse were 1310 mg/kg and 3000 mg/kg, respectively [5]. Subcutaneous LD50 in rat was 70 mg/kg [5].

The main target organs of camphor are the CNS and kidneys. Camphor is a CNS stimulant that may cause convulsions, depression, apnea, asystole, gastric irritation, colic, nausea, vomiting, diarrhea, anxiety, excitement, delirium, and severe post-convulsive coma [5]. Camphor is also irritating to the eyes, skin and mucous membranes following dermal contact of high doses. Gastrointestinal irritation and CNS depression may occur at doses over 10 mg/kg while as little as 1 g has been fatal in infants, and death has been reported with doses of 50 mg/kg or more [5]. There is no known antidote for camphor intoxication, thus gastrointestinal decontamination via activated charcoal is generally recommended for oral camphor overdose [5].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. 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. doi: 10.1523/JNEUROSCI.2574-05.2005. [PubMed:16192383]
  2. Selescu T, Ciobanu AC, Dobre C, Reid G, Babes A: Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin. Chem Senses. 2013 Sep;38(7):563-75. doi: 10.1093/chemse/bjt027. Epub 2013 Jul 4. [PubMed:23828908]
  3. Sherkheli MA, Vogt-Eisele AK, Weber K, Hatt H: Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues. Pak J Pharm Sci. 2013 May;26(3):431-8. [PubMed:23625413]
  4. Gyoubu K, Miyazawa M: In vitro metabolism of (-)-camphor using human liver microsomes and CYP2A6. Biol Pharm Bull. 2007 Feb;30(2):230-3. [PubMed:17268056]
  5. CAMPHOR - National Library of Medicine HSDB Database [Link]
External Links
KEGG Compound
C00809
ChemSpider
392267
ChEBI
15397
ChEMBL
CHEMBL2252949
MSDS
Download (48.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionTopical
OintmentTopical
CreamTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178-180MSDS
boiling point (°C)204MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.88 mg/mLALOGPS
logP2.85ALOGPS
logP2.55ChemAxon
logS-2.2ALOGPS
pKa (Strongest Basic)-7.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.07 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity44.49 m3·mol-1ChemAxon
Polarizability17.73 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - EI-BGC-MSsplash10-0zfr-3900000000-f7126616e4f1ddd0b8e1
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as bicyclic monoterpenoids. These are monoterpenoids containing exactly 2 rings, which are fused to each other.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Monoterpenoids
Direct Parent
Bicyclic monoterpenoids
Alternative Parents
Ketones / Organic oxides / Hydrocarbon derivatives
Substituents
Bicyclic monoterpenoid / Bornane monoterpenoid / Ketone / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Carbonyl group / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
camphor (CHEBI:15397)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
Activator
General Function
Transmembrane signaling receptor activity
Specific Function
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular aci...
Gene Name
TRPV1
Uniprot ID
Q8NER1
Uniprot Name
Transient receptor potential cation channel subfamily V member 1
Molecular Weight
94955.33 Da
References
  1. 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. doi: 10.1523/JNEUROSCI.2574-05.2005. [PubMed:16192383]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
Activator
General Function
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 d...
Gene Name
TRPV3
Uniprot ID
Q8NET8
Uniprot Name
Transient receptor potential cation channel subfamily V member 3
Molecular Weight
90635.115 Da
References
  1. 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. doi: 10.1523/JNEUROSCI.2574-05.2005. [PubMed:16192383]
  2. Sherkheli MA, Vogt-Eisele AK, Weber K, Hatt H: Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues. Pak J Pharm Sci. 2013 May;26(3):431-8. [PubMed:23625413]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Temperature-gated cation channel activity
Specific Function
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in t...
Gene Name
TRPA1
Uniprot ID
O75762
Uniprot Name
Transient receptor potential cation channel subfamily A member 1
Molecular Weight
127499.88 Da
References
  1. 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. doi: 10.1523/JNEUROSCI.2574-05.2005. [PubMed:16192383]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
General Function
Calcium 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, eucalypto...
Gene Name
TRPM8
Uniprot ID
Q7Z2W7
Uniprot Name
Transient receptor potential cation channel subfamily M member 8
Molecular Weight
127684.035 Da
References
  1. Selescu T, Ciobanu AC, Dobre C, Reid G, Babes A: Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin. Chem Senses. 2013 Sep;38(7):563-75. doi: 10.1093/chemse/bjt027. Epub 2013 Jul 4. [PubMed:23828908]

Drug created on December 03, 2015 09:52 / Updated on October 01, 2018 14:58