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Camphor: Benefits and risks of a widely used natural product

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 Volume 53(2):77-82, 2009
Acta Biologica Szegediensis
http://www.sci.u-szeged.hu/ABS

REVIEW

Camphor: benefits and risks of a widely used natural

product
Paolo Zuccarini1*, Giulio Soldani2

Department of Crop Biology, Sect. Plant Physiology, University of Pisa, Pisa, Italy, 2Department of Veterinary Clinics,
1

University of Pisa, Pisa, Italy

ABSTRACT The main aspects of the non-clinical profile of D-camphor, a natural product KEY WORDS
widely used as a common remedy for several symptoms, are reviewed. The pharmacodynamics
D-camphor
and toxicity of this substance are analyzed, with regard to all the literature available, in order pharmacodynamic
to assess a risk profile and better understand the positive and negative results connected with pharmacokinetics
its use. The general conclusion is that the main risks of camphor as a medicinal product are risk/benefit assessment
mainly due to a somehow diffused attitude of considering it as “not a real medicine”, and to toxicity
its consequent sometimes not sufficiently careful administration.
Acta Biol Szeged 53(2):77-82 (2009)

Camphor (Figure 1) is a natural product deriving from the Pharmacology

wood of the camphor laurel (Cinnamomum camphora L.)
Pharmacodynamics
trees through steam distillation and puriÞcation by sublimi-
nation; the trees used should be at least 50 years old. It also Camphor, a natural product derived from the wood of the tree
occurs in some other related trees in the laurel family, notably Cinnamomum camphora, has a long history of use as anti-
Ocotea usambarensis Eng., and can also be obtained from septic, analgesic, antipruritic, counterirritant and rubefacient
the plant Lippia dulcis Trev., but this is not a major industrial (Hercogov‡ 2005; Lynde et al. 2008). Its success and wide
source (Compadre et al. 1986). A major source of camphor in medical use, especially in topical preparations, is connected
Asia is Ocimum kilimandscharicum Baker ex Gurke. to its mild local anesthesizing effect and to the production
Camphor can also be produced synthetically from vinyl of a circumscribed sensation of heat, together with its char-
chloride and cyclopentadiene, passing through the intermedi- acteristic and penetrating odour that is by most of people
ate dehydronorbornyl chloride. The naturally occurring form associated to the idea of a strong and effective medicine
is dextrorotatory and the synthetic form optically inactive (Gibson et al. 1989).
(Budavari 1989; Reynolds 1989). Camphor is today mostly used in the form of inhalants and
Camphor has a counterirritant, rubefacient and mild of camphorated oil, a preparation of 19% or 20% camphor
analgesic action, and is a major component of liniments for in a carrier oil, for the home treatment of colds (Jochen and
relief of Þbrositis, neuralgia and similar conditions. It can be Theis 1995) and as a major active ingredient of liniments and
used as a mild expectorant; if ingested, camphor has irritant balms used as topical analgesics (Xu et al. 2005).
and carminative properties. Camphorated-oil, a solution in The antitussive, nasal decongestant and expectorant action
oil given through intramuscular or subcutaneous way, can be of camphor and of its derivatives was one of the Þrst ones to
used as a circulatory and respiratory stimulant, but this use is be systematically investigated (Inoue and Takeuchi 1969).
considered hazardous. When, in combination with menthol Its nasal decongesting activity seems to be not purely me-
and chenodeoxycholic acid, it has been used to aid dispersal chanic, but connected with the stimulation of cold receptors
of bile duct stones, although this is no longer recommended in the nose. The inhalation of camphor vapours (so as the one
(Reynolds 1989). of eucalyptus and menthol vapours) on a sample of volunteers
Aim of the present work is to provide an overview over increased the nasal sensation of airßow through the induction
pharmacological and toxicological aspects of camphor, in of cold sensation in the nose, despite of actually not affecting
order to assess its safety proÞle and evaluate the level of risk nasal resistance to airßow (Burrow et al. 1983).
connected with its use. More recent studies pointed out how camphor efÞcacy
in the treatment of cold is due to its antispasmodic action
(Astudillo et al. 2004), and how the effects of camphor on
Accepted Oct 20, 2009 bronchospasm are connected to its anti-histaminergic and
*Corresponding author. E-mail: p.zuccarini@virgilio.it anti-cholinergic activities (Gšrnemann et al. 2008). In fact,

77
Zuccarini, Soldani

clariÞed activity of camphor as a TRPA1 inhibitor has been

utilized by Lee et al. (2008) for pretreatment of human em-
bryonic kidney cells tested for membrane potential changes
elicited by thymol, showing how the response to thymol is
blocked by camphor. Bang et al. (2007) showed camphor
to suppress acute pain in mouse consequent to intradermal
administration of acetaldehyde into mouse footpads.
Capsaicin shares the same action with camphor, but per-
forms it more slowly and less completely; on the other side
camphor efÞcacy is lower, since higher concentrations are
required (Xu et al. 2005). Studies on rats demonstrated that
the actions of capsaicin and camphor are segregated (Wu et
al. 2005), i.e. they are mediated by distinct channel regions,
Figure 1. Structural formula of Camphor, a bicyclic monoterpene ketone and camphor did not activate TRPV1 in capsaicin-insensitive
(1,7,7-trimethylbicyclo [2.2.1] heptan).
chickens (Xu et al. 2005; Jordt and Julius 2002).
Camphor also inhibits other related TRP channels such as
ankyrin-repeat TRP1 (TRPA1), which is a further evidence
camphor appears to be effective to reduce histamine H1 and underlying its analgesic effects (Xu et al. 2005).
muscarinic M3 receptor-mediated bronchocostriction (Gšrne- Camphor was shown to inhibit mitochondrial respiration.
mann et al. 2008), and this action relates also to the inhibition Administration of up to 8 µM of camphor inhibited respira-
of cough (Kreutner et al. 2000). tion rate in rat-liver mitochondria, nearly halving the oxygen
Camphor was administered in the form of aromatic vapor, consumption; this suggests that camphor may be used in oxy-
at the concentrations of 50, 133 and 500 µg l-1, to guinea pigs genating tumors prior to radiotherapy (Guilland-Cumming
subject to chemically induced cough. No effect were regis- and Smith 1979; 1982).
tered at the lowest concentrations, but 500 µg l-1 camphor gave Camphor can also be a potential radiosensitizing agent
a 33% reduction of cough frequency, to which an increase in in radiotherapy. Treatment with camphor (0.5 µmol á body
cough latency coincided (Laude et al. 1994). wt-1) 45 minutes before local x-irradiation at the dose levels
The analgesic proprieties of camphor are largely known of 30, 80, 100 or 120 Gy was performed on male C3H/Jax
and applied, but little is known about the molecular mecha- mice bearing transplanted mammary tumours. Sequential
nisms that are at their basis. (Xu et al. 2005). measurement of the tumour volumes during 45 days after the
Moqrich et al. (2005) demonstrated that camphor activates irradiation revealed a 4.8 delay of the maximum enhancement
TRPV3, a member of transient receptor channel superfamily, ratios in tumour growth (Goel and Roa 1988).
leading to excitation and desensitization of sensory nerves. D-camphor (1100 µg ml-1) inhibited oxidative metabolism
The notorious effect of generation of a sensation of heath in E.coli (Cardullo and Gilroy 1975). Succinic, lactic and
associated with topic application of camphor (Green 1990) NADH-oxidase activities were inhibited, while NADH and
is a consequence of this activation. In fact, TRPV3 is a warm- succinic DCPIP oxidoreductase enzymes were unaffected.
sensitive Ca2+-permeable cation channel, that once activated The restoration of succinic oxidase activity by ubiquinone
originates the warm sensation, actually simulating an effective (Q6) but not by vitamin K1 indicates that D-camphor may
increase of temperature in the treated area (Xu et al. 2006). operate this inhibition by affecting quinone functions.
This effect, caused by an increase in intracellular Ca2+ lev-
els, is typical also of other natural compounds as carvacrol, Pharmacokinetics
eugenol and thymol (Xu et al. 2006). Camphor is readily absorbed from all the sites of administra-
Anyway excessive and repeated application of camphor tion, after inhalation, ingestion or dermal exposure (Baselt
can lead to sensibilization of TRPV3, in apparent contrast and Cravey 1990). Peak plasma levels were reached by 3
with its analgesic role (Peier et al. 2002; Moqrich et al. hours post-ingestion when 200 mg camphor was taken alone,
2005). and 1 hour post-ingestion when it was ingested with a solvent
The antipruritic and counterirritant activity of camphor (Tween 80; Koppel et al. 1988).
is instead associated with its capacity of activating TRPV1 In case of dermal application, the volume of the absorp-
- another member of TRP channel superfamily - at the level tion is relatively low in comparison with the speed of the
of dorsal root gangliar [DRG] neurons and inhibiting TRPA1 process. After application of different numbers of commercial
channels (Moqrich et al. 2005; Nagata et al. 2005), action patches [2, 4 or 8] to the skin of human subjects during 8
that is in common with other TRPV1 agonists (Bhave et al. hours, the levels of camphor in the plasma were assayed with
2002; Xu et al. 2006; Belmonte and Viana 2008). The recently selective gas-cromatography (Valdez et al. 1999; Martin et

78
 Camphor: its beneÞts and risks

al. 2004). Maximum camphor plasma concentration resulted aryl-hydrocarbon hydroxylase and glutathione S-transferase,
in a range between 35.2 and 46.8 ng/ml-1 in the case of 8 signiÞcantly elevating the level of reduced glutathione in the
patches, between 19.6 and 34 ng/ml-1 for the 4 patches while liver (Banerjee et al. 1995).
almost undetectable concentrations were observed when only
2 patches had been applied, showing that dermal absorption Interactions
is prompt but not massive. Very few studies of pharmacological interactions between
Camphor is distributed throughout the whole body, and camphor and other compounds are present in literature. In a
can permeate the placenta; for this reason it must be recom- study combining the administration of D-camphor and an ex-
mended that the use of this product is avoided during preg- tract from fresh crataegus berries, a synergic action of the two
nancy and lactation (Sweetman 2005). preparations emerged in ameliorating cardiac performances.
Its volume of distribution is 2-4 L/kg (Koppel et al. 1988); Both D-camphor and the extract contributed in an increase
plasma protein binding has been estimated as 61% (Koppel in total peripheral resistance induced by an increase tone of
et al. 1982). the arterioles, and while the former appeared to be the main
After its absorption and distribution, camphor undergoes factor in inducing the rapid initial effect, the former added a
hepatic metabolism: it is hydroxylated in the liver into hy- long-lasting effect (Belz and Loew 2003).
droxycamphor metabolites (Sweetman 2005).
Asahina and Ishidate (1933; 1934; 1935) isolated cis- Toxicity
and trans-¹-hydroxycamphor and camphor-¹-carboxylic
acid from the urine of dogs that had been fed with camphor; Camphor occurs in nature in its dextrorotatory form (D-
Shimamoto (1934) obtained 3-hydroxycamphor (15%), camphor), while the laevorotatory form (L-camphor) exists
5-hydroxycamphor (55%) and trans-¹-hydroxycamphor only as a synthetic form. The two enantiomers present dif-
(20%) from the urine of dogs, and 5-hydroxycamphor [as ferent proÞles of toxicity.
major metabolite] and 3-hydroxycamphor from the urine of D-camphor, L-camphor and their racemic mixture were
rabbits. tested for toxicity in mice. At 100 mg á Kg b.w.-1 the natural
Robertson and Hussain (1969) observed that (+)-cam- form was non toxic, while the synthetic form induced differ-
phor and (-)-camphor increase the content of glucuronide ent kinds of toxic and behavioural effects such as body jerks
in the urine of rabbits; (+)-camphor was moreover reduced and hunched posture; the racemic mixture showed similar
to (+)-borneol as well as being hydroxylated to (+)-5-endo- effects to the L-form (Chatterjie and Alexander 1986).
hydroxycamphor [major product] and (+)-3-endo-hydroxyc- The oral administration of acute doses of D-camphor to
amphor. rats and rabbits caused pronounced signs of toxicity. In rats,
Hydroxylation of camphor, as well as norcamphor, peri- the consume of food was reduced proportionally to the ad-
cyclocamphanone and 5,5-dißuorocamphor, is mainly per- ministered dose, starting from 464 mg á Kg b.w.-1 á day-1, and
formed by cytochrome P450 (Collins and Loew 1988), a class at 1000 mg á Kg b.w.-1 á day-1 convulsions and pilo-erection
of heme-containing monooxygenases that are distributed in were observed, connected with a reduction of motility and
the whole body (Boxenbaum 1984), by hydrogen abstraction weight gain. Reduced body weight gain and food consump-
(Wand and Thompson 1986). Cytochrome P450 is responsible tion were observed in rabbits treated with 681 mg á Kg b.w.-1
for camphor conversion into 5-hydroxycamphor (Gelb et al. á day-1 (Leuschner 1997).
1982), while 3-hydroxycamphor is the primary product of Camphor showed porphyrogenic activity in primary cul-
non-enzymatic hydroxylation of camphor (Land and Swallow tures of chick embryo - liver cells, with enhanced porphyrin
1979). Camphor hydroxylation by cytochrome P450 occurs accumulation ranging from 5- to 20-fold (Bonkovsky et al.
with a different region-speciÞcity for camphor and its related 1992).
compounds (Collins and Loew 1988). The main problems about camphor toxicity in humans
Hydroxylated metabolites are then conjugated with are connected more to the large availability of camphor-
glucuronic acid and excreted in the urine (Sweetman 2005). containing products and their diffused perception as un-
The half-life of 200 mg of camphor was 167 minutes when hazardous medicines rather than in the intrinsic toxicity of
ingested alone, and 93 minutes when ingested with a solvent camphor. The daily maximum human therapeutic dose is in
(Tween 80) (Koppel et al. 1988). fact approximately 1.43 mg á Kg-1, which corresponds to a
Camphor can modulate the activities of hepatic enzymes therapeutic ratio of more than 450 for the endpoint toxicity,
involved in phase I and phase II drug metabolism. 50, 150 reßecting a wide margin of safety (Leuschner 1997). On the
and 300 mg/Kg-1 of camphor dissolved in 0.1 ml of olive oil other side, as mentioned above, camphor is present in several
was administered daily to female Swiss Albino mice during over-the-counter products, its use as a familiar remedy is com-
20 days. At its highest concentration it caused a signiÞcant monly accepted, but still some lack of information persists
increase in the activities of cytochrome P450, cytochrome b5, among the consumers.

79
Zuccarini, Soldani

Cases of camphor intoxication in humans, especially Camphor has also an important role in the treatment of
children, are relatively frequent, mostly because of accidental cough and colds thanks to its antispasmodic activity, due to
ingestion (Siegel and Wason 1986). More than 100000 cases anti-histaminergic and anti-cholinergic action that causes
of ingestion exposures to camphor-containing products were depression of bronchospasm coupled with inhibition of
registered between 1990 and 2003 (Manoguerra et al. 2006), cough.
causing a range of symptoms that comprises convulsion, This compound has also a long history of scientiÞc studies
lethargy, ataxia, severe nausea, vomiting and coma (Koppel on its action and on the way through which it is metabolized
et al. 1988; Manoguerra et al. 2006). in the organisms of both humans and animals, due to the
general interest that it has always arisen among common
Reproduction toxicity people and scientists. Already in 1879, Schmeideberg and
D-camphor was orally administered to pregnant rats and Meyer were analyzing the metabolites isolated from the urine
rabbits during the period of organogenesis to test its embryo- of dogs that had been fed with (+/-) camphor (Schmiedeberg
toxicity. Doses up to 1000 mg á Kg b.w.-1 á day-1 to rats and up and Meyer 1879), and during the Þrst half of the twentieth
to 681 mg á Kg b.w.-1 á day-1 to rabbits showed no teratogenic century the number of studies focused on its pharmacology
effects, and in none of the animals were observed higher rates and pharmacokinetics has been remarkable.
of mutations or malformations (Leuschner 1997). The bibliographic search that was performed for the com-
pilation of this toxico-pharmacological overview revealed a
Mutagenicity and cancerogenicity rich literature existing on camphor, and put in evidence the
large amount of works focused on toxic aspects of camphor
In a Salmonella/microsome assay, the upper limit of the dose that were published during the last 30 years; a great number
interval tested for (+/-) camphor resulted to be the highest of reports concerning cases of camphor intoxication were also
non-toxic dose, suggesting that the compound is not muta- collected. In most cases camphor intoxication occurred fol-
genic in the Ames test (Gomes-Carneiro et al. 1998). lowing accidental ingestion of camphor-containing product,
A single dose of camphor (0.5 µM á g-1) administered 30, and sometimes lethal episodes of intoxication of infants due
45 or 60 minutes before gamma irradiation signiÞcantly re- to application of camphor to their nostrils were collected.
duced the frequency of sister-chromatid exchanges in mouse As it emerges from all the observed data the toxic risks of
bone marrow, showing therefore a radiomodifying inßuence camphor-containing products in general, and of camphorated
(Goel at al. 1989). oil in particular, are connected essentially with its improper
uses, e.g. accidental ingestion, but camphor does not repre-
Discussion and Conclusions sent a threaten for safety when used on the target patients,
Camphor is familiar to many people as a principal ingredient following the indicated dosages and the contraindications.
in topical home remedies for a wide range of symptoms, and Special care must be taken during pregnancy, due to the fact
its use is well consolidated among the population of the whole that camphor crosses the placental barrier, and camphor and
world, having a long tradition of use as antiseptic, antipruritic, camphor containing products should be avoided in children
rubefacient, abortifacient, aphrodisiac, contraceptive and who have a history of febrile convulsions or other predispos-
lactation suppressant. ing factors for convulsions (Galland et al. 1992).
In particular, the analgesic and antipruritic action of In the past, when camphor was used medicinally, the
the compound make it appreciated by a large number of oral doses ranged from 120-300 mg (Wade 1977), and the
consumers, by whom it is used in the form of essential oil parenteral dose range was from 60-200 mg (not recommended
for cutaneous application. Itch is a complex phenomenon, anymore).
being difÞcult to localize and quantify (Wahlgren 1995) and Camphorated oil can be used with no risks for safety when
involving a variety of skin surface receptors, peripheral and following the prescriptions. The relatively diffused tendency
central nerves and speciÞc brain regions. The treatment of to the improper use of camphor (high dosages, accidental
itch usually relies on antisthamines, corticoids or various ingestion, use on infants) is connected with the perception
topical remedies (Langner and Maibach 2009) among which of the product, by many consumers, as a sort of ÒpanaceaÓ
camphor has a prominent role. The analgesic action is due to with no contraindication. More and more accessible informa-
its interacions with members of TRP channel superfamily tion is therefore necessary to bring to a ÒresponsabilizationÓ
Camphor is therefore an important remedy for symptom- of the consume of this product, in order to avoid hazardous
atic treatment of itching, especially in patients affected by situations.
contact dermatitis, because it goes to affect directly the cuta- All the above considerations allow the conclusion that
neous nerve ending, as other agents like pramoxine, phenol camphor in its form of camphorated oil can be safely used
and menthol do (Burkhart and Burkhart 2003). at the proposed dosages, on the indicated patients target, for
topic application.

80
 Camphor: its beneÞts and risks

Acknowledgements Med 7:41-43.

Goel HC, Roa AR (1988) Radiosensitizing effect of camphor on transplant-
The Authors would like to thank Annie Hart (A.R.S.) and able mammary adenocarcinoma in mice. Cancer Lett 43(1-2):21-27.
Marina Ribatski (B.D.R.) for useful help during the elabora- Goel HC, Singh S, Singh SP (1989) Radiomodifying inßuence of camphor
on sister-chromatid exchange induction in mouse bone marrow. Mutat
tion of the manuscript. Res 224(2):157-160.
Gšrnemann T, Nayal R, Peretz HH, Melzig MF (2008) Antispasmodic
References activity of essential oil from Lippia dulcis Trev. J Ethnopharmacol
117:166-169.
Asahina Y, Ishidate M (1933) Ber dtsch chem Ges 67:71. Green BG (1990) Sensory characteristics of camphor. J Invest Dermatol
Asahina Y, Ishidate M (1934) Ber. dtsch. chem. Ges 68B:967. 94(5):662-666.
Asahina Y, Ishidate M (1935) Ber dtsch chem Ges 69:349. Gomes-Carneiro MR, Felzenszwalb I, Paumgartten FJ (1998) Mutagenicity
Astudillo A, Hong E, Bye R, Navaretta A (2004) Antispasmodic activity of testing (+/-)-camphor, 1,8-cineole, citral, citronellal, (-)-menthol and
Acalypha phleoides Cav. Phytother Res 18:102-106. terpineol with the Salmonella/microsome assay. Mutat Res 416(1-2):
Banerjee S, Welsch CW, Rao AR (1995) Modulatory inßuence of camphor 129-136.
on the activities of hepatic carcinogen metabolizing enzymes and the Guilland-Cumming D, Smith GJ (1979) Mitochondrial respiration depressed
levels of hepatic and extrahepatic reduced glutathione in mice. Cancer by camphor: a possible aid in radiotherapy. Experientia 35(5):659.
Letters 88(2):163-169. Guilland-Cumming DF, Smith GJ (1982) The effect of camphor on mito-
Bang S, Kim KY, Yoo S, Kim YG, Hwang SW (2007) Transient receptor chondrial respiration. Experientia 38(2):236-237.
potential A1 mediates acetaldehyde-evoked pain sensation. European Hercogov‡ J (2005) Topical anti-itch therapy. Dermatol Ther 18:341-343.
Journal of Neurosciences 26:2516-2523. Inoue Y, Takeuchi S (1969) Expectorant-like action of camphor derivatives.
Baselt RC, Cravey RH (1990) Disposition of toxic drugs and chemicals and Nippon Ika Daigaku Zasshi 36(4):351-354.
drugs 3rd ed. Year Book Medical Publishers Inc. Land EJ, Swallow AJ (1979) Some free radical reactions of camphor in rela-
Belmonte C, Viana F (2008) Molecular and cellular limits to somatosensory tion to the action of cytochrome P450. Journal of the Chemical Society,
speciÞcity. Mol Pain 4:14-31. Faraday Transactions I 75:1849-1856.
Belz GG, Loew D (2003) Dose-response related efÞcacy in orthostatic Langner MD, Maibach HI (2009) Pruritus measurement and treatment. Clin
hypotension of a Þxed combination of D-camphor and an extract from Exp Dermatol 34:285-288.
fresh crataegus berries and the contribution of the single components. Laude EA, Morice AH, Grattan TJ (1994) The antitussive effects of men-
Phytomedicine 4:61-67. thol, camphor and cineole in conscious guinea-pigs. Pulm Pharmacol
Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW (2002) 7(3):179-184.
cAMP-dependent protein kinase regulates desensitization of the capsai- Lee SP, Buber MT, Yang Q, Cerne R, CortŽs RY, Sprous DG, Bryant RW
cin receptor (VR1) by direct phosphorylation. Neuron 35(4):721-731. (2008) Thymol and related alkyl phenols activate the hTRPA1 channel.
Bonkovsky HL, Cable EE, Cable JW, Donohue SE, White EC, Greene YJ, Br J Pharmacol 153:1739-1749.
Lambrecht RW, Srivastava KK, Arnold WN (1992) Porphyrogenic Leuschner J (1997) Reproductive toxicity studies of D-camphor in rats and
properties of the terpenes camphor, pinene, and thujone (with a note on rabbits. Arzneimittelforschung 47(2):124-128.
historic implications for absinthe and the illness of Vincent van Gogh). Jochen GW, Theis MD (1995) Camphorated oil: still endangering the lives
Biochem Pharmacol 43(11):2359-2368. of Canadian children. Can Med Assoc J 152(11):1821-1824.
Boxenbaum H (1984) Interspecies Pharmacokinetic Scaling and the Evolu- Jordt SE, Julius D (2002) Molecular basis for species-speciÞc sensitivity to
tionary-Comparative Paradigm. Drug Metab Rev 15:1071-1121. ÒhotÓ chili peppers. Cell 108(3):421-430.
Budavari S (Ed.), (1989) The Merck Index. 11th Edition. Merck and Co Koppel C, Tenczer J, Schirop T, Ibe K (1982) Camphor poisoning - abuse of
Inc, Rahway, USA. camphor as a stimulant. Arch Toxicol 51:101-106.
Burkhart CG, Burkhart HR (2003) Contact irritant dermatitis and anti-pruritic Koppel C, Martens F, Schirop Th, Ibe K (1988) Hemoperfusion in acute
agents: the need to address the itch. J Drugs Dermatol 2(2):143-146. camphor poisoning. Intensive Care Medicine 14:431-433.
Burrow A, Eccles R, Jones AS (1983) The effects of camphor, eucalyptus Kreutner W, Hey JA, Anthes J, Barnett A, Young S, Tozzi A (2000) Preclinical
and menthol vapour on nasal resistance to airßow and nasal sensation. pharmacology of desloratadine, a selective and nonsedating histamine
Acta Otolaryngologica 96(1-2):157-161. H1 receptor antagonist. Arzneimittel forschung 50:345-352.
Cardullo MA, Gilroy JJ (1975) Inhibition of oxidative metabolism in Escheri- Lynde CB, Kraft JN, Lynde CW (2008) Novel agents for intractable itch.
chia coli by d-camphor and restoration of oxidase activity by quinones. Skin Therapy Letters 13(1):6-9.
Can J Microbiol 21(9):1357-1361. Manoguerra AS, Erdman AR, Wax PM, Nelson LS, Caravati EM, Cobaugh
Chatterjie N, Alexander GJ (1986) Anticonvulsant properties of spirohy- DJ, Chyka PA, Olson KR, Booze LL, Woolf AD, Keyes DC, Christian-
dantoins derived from optical isomers of camphor. Neurochem Res son G, Scharman EJ, Troutman WG (2006) Camphor Poisoning: an
11(12):1669-1676. evidence-based practice guideline for out-of-hospital management. Clin
Collins JR, Loew GH (1988) Theoretical study of the product speciÞcity Toxicol (Phila) 44(4):357-370.
in the hydroxylation of camphor, norcamphor, 5,5-dißuorocamphor, Martin D, Valdez JS, Boren J, Mayersohn M (2004) Dermal absorption of
and pericyclocamphanone by cytochrome P450cam. J Biol Chem camphor, menthol, and methyl salicylate in humans. J Clin Pharmacol
263(7):3164-3170. 44(10):1151-1157.
Compadre CM, Robbins EF, Kinghorn AD (1986) The intensely sweet herb, Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS,
Lippia dulcis Trev.: historical uses, Þeld enquiries, and constituents. J Andahazy M, Story GM, Patapoutian A (2005) Impaired thermosensa-
Ethnopharmacol 15(1):89-106. tion in mice lacking TRPV3, a heat and camphor sensor in the skin.
Galland MC, Griguer Y, Morange-Sala S, Jean-Pastor MJ, Rodor F, Jouglard Science 307(5714):1468-1472.
J (1992) Convulsions febriles: faut-il contre-indiquer certains medica- Reynolds JEF (Ed.), (1989) Martindale The Extra Pharmacopeia. 29th edi-
ments? Therapie 47(5):409-414. tion. The Pharmaceutical Press, London.
Gelb MH, Heimbrook DC, Miilkonen P, Sligar SG (1982) Stereochemistry Nagata K, Duggan A, Kumar G, Garcia-Anoveros J (2005) Nociceptor and
and deuterium isotope effects in camphor hydroxylation by the cyto- hair cell transducer properties of TRPA1, a channel for pain and hearing.
chrome P450cam monooxygenase system. Biochemistry 21(2):370- J Neurosci 25(16):4052-4061.
377. Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC,
Gibson DE, Moore GP, Pfaff JA (1989) Camphor ingestion. Am J Emerg Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian

81
 Zuccarini, Soldani

A (2002) A heat-sensitive TRP channel expressed in keratinocytes. Appl 729(1-2):163-171.

Science 296:2046-2049. Wade A (ed.) (1977) Martindale The Extra Pharmacopeia. 27th edition. The
Robertson JS, Hussain M (1969) Metabolism of camphors and related com- Pharmaceutical Press, London.
pounds. Biochemical Journal 113(1):57-65. Wahlgren CF (1995) Measurement of itch. Semin Dermatol 14:277-284.
Schmiedeberg O, Meyer H (1879) Hoppe-Seyl Z 3:422. Wand MD, Thompson JA (1986) Cytochrome P450-catalyzed rearrangement
Shimamoto T (1934) Sci Pap Iet Phye Chem Res, Tokyo 529:52-58, 59- of a peroxyquinol derived from butylated hydroxytoluene. Involvement
62. of radical and cationic intermediates. J Biol Chem 261:14049-14056.
Siegel E, Wason S (1986) Camphor toxicity. Pediatr Clin North Am Xu H, Blair NT, Clapham DE (2005) Camphor activates and strongly desen-
33(2):375-379. sitizes the transient receptor potential vanilloid subtype 1 channel in a
Sweetman SC (ed.), (2005) Martindale: The Complete Drug Reference. 34th vanilloid-independent mechanism. J Neurosci 25(39):8924-8937.
edition. The Pharmaceutical Press, London. Xu H, Delling M, Jun JC, Clapham DE (2006) Oregano, thyme and clove-
Valdez JS, Martin DK, Mayersohn M (1999) Sensitive and selective gas derived ßavors and skin sensitizers activate speciÞc TRP channels. Nat
chromatographic methods for the quantitation of camphor, menthol Neurosci 9:628-635.
and methyl salicylate from human plasma. J Chromatogr B Biomed Sci

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