Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Menthol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2006

Effects of capsaicin and menthol on oral thermal sensory thresholds.

OBJECTIVE: To determine the long-term effect of capsaicin and short-term effect of menthol on oral thermal thresholds. DESIGN: The thresholds for cold detection (CDT), warm detection (WDT), cold pain (CPT) and warm pain (WPT) were determined in 11 regular chilli-eaters (capsaicin group) and 11 control subjects that were closely matched for age, gender and ethnicity. The effect of menthol was determined by asking all 22 participants to suck a lozenge containing 0.52% menthol for 5min. RESULTS: An ANOVA revealed a significant difference between the capsaicin and control groups (P=0.014), with the greatest difference in the WDT (capsaicin group 4.7+/-2.7[S.D.] degrees C; control group 2.3+/-2.2 degrees C). Immediately after sucking a menthol lozenge there was a significant rise in the CDT (2.2+/-1.1 degrees C to 5.9+/-6.2 degrees C; P<0.01) and WDT (3.6+/-2.7 degrees C to 7.6+/-4.4 degrees C; P<0.001). CONCLUSIONS: The consumption of foods containing capsaicin and menthol significantly alters thermal sensory thresholds in the oral cavity. Dietary habits should therefore be taken into account when intra-oral thermal thresholds are determined.

Adult↗
PubMed2005

Biophysical properties of menthol-activated cold receptor TRPM8 channels.

The temperature-sensitive transient receptor potential channel, TRPM8, was recently cloned and found to be activated by cold and menthol. Whole-cell recordings show that TRPM8 is permeable to multiple cations and exhibits a strong outward rectification. Here, we examine the mechanism underlying menthol-evoked current rectification of TRPM8 transiently expressed in tsA-201 cells at room temperature ( approximately 25 degrees C). Whole-cell currents (ruptured, bath: Na(+), K(+), Ca(2+), or Ba(2+); pipette: KCl) exhibited a strong outward rectification in the presence of menthol, consistent with previous studies. The outward K(+) current was reduced in the presence of external Ca(2+) or Ba(2+). Single-channel recordings (cell-attached) showed that menthol induced brief channel openings with two conducting states in the voltage range between -80 and +60mV. The small current (i(S)) conducted both monovalent and divalent ions, and the large one (i(L)) predominantly monovalent ions. The i-V plot for Ca(2+) was weakly outward rectifying, whereas those for monovalent ions were linear. The i(S) may result in the divalent ion-induced reduction of the whole-cell outward current. The open probability (P(o)) in all ion conditions tested was low at negative voltages and increased with depolarization, accounting for the small inward currents observed at the whole-cell level. In conclusion, our results indicate that menthol induced steep outward rectification of TRPM8 results from the voltage-dependent open channel probability and the permeating ion-dependent modulation of the unitary channel conductance.

Cell Line↗
PubMed2004

Determination of menthol in plasma and urine of rats and humans by headspace solid phase microextraction and gas chromatography--mass spectrometry.

A method for the determination of menthol and menthol glucuronide (M-G) after enzymatic hydrolysis in plasma and urine of rats and humans was developed using headspace solid phase microextraction and gas chromatography-mass spectrometry in the selected ion monitoring mode (HS-SPME/GC-MS). The assay linearity for plasma ranged from 5 to 1000 ng/ml. The limit of quantification (LOQ) in plasma was 5 ng/ml. The intra- and inter-day precision for menthol and M-G were < or = 18.1% R.S.D. at the LOQ and < or = 4.0% at higher concentrations. Menthol and M-G were determined in rat and human plasma and urine after administration of menthol.

Animals↗
PubMed1997

13-week inhalation toxicity study of menthol cigarette smoke.

Menthol is a common pharmaceutical, food and tobacco flavouring ingredient used for its minty characteristics and cooling effects. A 13-wk comparative nose-only smoke inhalation toxicity study was conducted using an American-style, cellulose acetate-filtered, non-menthol reference cigarette and a similarly blended test cigarette containing 5000 ppm synthetic l-menthol tobacco. Male and female Fischer 344 rats were exposed for 1 hr/day, 5 days/wk for 13 wk at target mainstream smoke particulate concentrations of 200, 600 or 1200 mg/m3, while control rats were exposed to filtered air. Internal dose biomarkers (blood carboxyhaemoglobin, serum nicotine and serum continine) indicated equivalent exposures were obtained for the two cigarettes. Effects typically noted in rats exposed to high levels of mainstream tobacco smoke were similar for both cigarette types and included reduced body weights (males slightly more affected than females), increased heart-to-body weight ratios and lung weights, and histopathological changes in the respiratory tract. Rats exposed to reference cigarette smoke displayed a dose-related increase in nasal discharge that was not observed in menthol smoke-exposed rats. All smoke-related effects diminished significantly during a 6-wk non-exposure recovery period. The results of this 13-wk smoke inhalation study indicated that the addition of 5000 ppm menthol to tobacco had no substantial effect on the character or extent of the biological responses normally associated with inhalation of mainstream cigarette smoke in rats.

Administration, Inhalation↗
PubMed1997

The effect of L-menthol stimulation of the major palatine nerve on subjective and objective nasal patency.

To determine whether L-menthol stimulation of the major palatine nerve can affect nasal patency, we noted subjective and measured objective nasal patency before and after L-menthol stimulation of the palatal mucosa. L-Menthol stimulation of the palatal mucosa enhanced nasal sensation of airflow but nasal resistance was unaffected. By contrast, L-menthol stimulation after local anesthesia of the palatine nerve or of the nasal mucosa substantially diminished the subjective response of increased nasal patency but without affecting objective nasal patency. It is suggested that the effect of both direct stimulation by L-menthol of the major palatine nerve and its vapor action on the sensory nerve endings of the nasal mucosa produce an increase in the sensation of nasal patency without an increase in objective nasal patency.

Administration, Oral↗
PubMed1983

The effect of menthol on nasal resistance to air flow.

Total nasal resistance to airflow was measured in thirty-one subjects before and after five minutes' exposure to menthol vapour. Menthol inhalation had no consistent effect on nasal resistance but the majority of subjects reported an increased sensation of nasal airflow and a cooling effect of menthol. The results indicate that menthol stimulates cold receptors in the nasal mucosa to create an increased sensation of airflow. No evidence was found in support of any nasal decongestant action for menthol.

Adult↗
PubMed1997

Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin.

The potential use of terpenes/terpenoids as penetration enhancers in the transdermal delivery of propranolol hydrochloride (PL) was investigated. PL was chosen for the reasons of its extensive first-pass metabolism and short elimination half-life. The terpenes studied included L-menthol, (+)-limonene, (+/-)-linalool, and carvacrol at 1%, 5%, and 10% w/v concentrations. The diffusion of PL across excised hairless mouse skin was determined using side-by-side diffusion cells. Flux, permeability coefficient (Pm), and lag time (tL) were calculated. PL showed comparable lag times with menthol at all three concentration levels. At a 1% level of carvacrol, PL exhibited a 2.4- and 2.2-fold increase in lag time compared with 5 and 10% levels of enhancer, respectively. In the presence of limonene, PL had shown maximum lag time (between 3.0 and 3.3 h) at all three levels. In the case of linalool, the lag times for PL with 5 and 10% levels of enhancer were 7.0- and 5.2-fold less compared with 1% level. A significant (p < 0.05) concentration effect was observed only with linalool. Hydrogel-based patches were formulated with or without menthol as enhancer. Release profiles from the hydrogel formulations obeyed zero-order kinetics. The permeability of propranolol was significantly higher (p < 0.05) from the test patch than the control (no enhancer) patch across the mouse skin. The mechanism of permeation enhancement of menthol could involve its distribution preferentially into the intercellular spaces of stratum corneum and the possible reversible disruption of the intercellular lipid domain. The results suggest the potential use of menthol as effective penetration enhancer in the delivery of significant amounts of PL through skin.

Acyclic Monoterpenes↗
PubMed1994

Analysis of the combined effect of 1-menthol and ethanol as skin permeation enhancers based on a two-layer skin model.

The combined effects of 1-menthol and ethanol as a skin permeation enhancer were evaluated with two equations describing the permeability coefficient through full-thickness skin (PFT) and the full-thickness skin/vehicle concentration ratio (CFT/CV) of drugs as a function of their octanol/vehicle partition coefficient (KOV). A two-layer model was applied for skin, which consists of a stratum corneum (SC) with lipid and porous pathways and a viable epidermis and dermis (ED). The two equations contain one variable (KOV) and nine coefficients, six of which (three diffusion coefficients, the porosity of the SC, and two terms of the linear free energy relationship) were considered different, dependent on the drug vehicle. In vitro permeation of four drugs (morphine hydrochloride, atenolol, nifedipine, and vinpocetine) was determined using excised hairless rat skin and four aqueous vehicles (water, 5% 1-menthol, 40% ethanol, and 5% 1-menthol-40% ethanol) to measure each PFT. Drug concentrations in full-thickness skin were also measured to obtain CFT/CV. A nonlinear least-squares method was employed to determine six coefficients using the two equations and experimentally obtained PFT and CFT/CV. The addition of 1-menthol to water and 40% ethanol increased the diffusion coefficient of drugs in lipid and pore pathways of SC, whereas the addition of ethanol to water and 5% 1-menthol increased the drug solubility in the vehicle, decreased the skin polarity, and increased the contribution of the pore pathway to whole-skin permeation.

Animals↗
PubMed2005

Permeation and reservoir formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the presence of ethanol and menthol.

Environmental influences may affect carcinogen absorption and residency in the tissues of the aero-digestive tract. We quantified the effect of ethanol and menthol on the rates of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) absorption using a fully validated in vitro diffusion system, capable of accurately and precisely quantifying tobacco carcinogen permeation and reservoir formation in porcine esophageal mucosa. Confocal microscopy was employed to visualize the location of B[a]P in the exposed membranes. Markedly different extents of permeation and reservoir formation for the tobacco carcinogens were recorded in the presence of ethanol and menthol. The water-soluble NNK permeated the membrane rapidly, while the lipophilic B[a]P did not appreciably diffuse through the tissue. Significantly different extents of reservoir formation were observed for the different carcinogens and in the presence of the different penetration-enhancer solvents. Alcohol (at 5% concentration) did not influence the permeation or reservoir formation of NNK. A mentholated donor solution (0.08%) both decreased the flux of NNK and significantly increased the tissue reservoir formation. The magnitude of the reservoir formed by B[a]P was relatively extensive (even though membrane permeation rates were negligible), being greatest in the presence of both ethanol and menthol. This suggests synergy between the two penetration-enhancer species acting on this carcinogen. Confocal microscopy studies confirmed that there was an appreciable intra-cellular, and specifically nuclear, association of the B[a]P species during the reservoir formation process. The aqueous solubility of the diffusing species and the presence of penetration enhancers appeared to be key factors in the absorption and cellular binding processes. The results presented support the hypothesis that the use of mentholated cigarettes, or the concomitant consumption of alcohol while smoking, may have marked effects on the fate of tobacco chemicals. This finding may help to explain elevated rates of esophageal squamous cell carcinoma in African Americans.

Animals↗
PubMed2003

Stimulation of bitterness by capsaicin and menthol: differences between lingual areas innervated by the glossopharyngeal and chorda tympani nerves.

Capsaicin is viewed as a purely chemesthetic stimulus that selectively stimulates the somatosensory system. Here we show that when applied to small areas of the tongue, capsaicin can produce a bitter taste as well as sensory irritation. In experiment 1, individuals were screened for the ability to perceive bitterness from capsaicin on the circumvallate papillae. Fifteen of 25 subjects who reported at least weak bitterness rated the intensity of taste, irritation and coolness produced by 100-320 microM capsaicin and 100-320 mM menthol applied via cotton swabs to the tip (fungiform region), the posterior edge (foliate region), and the dorsal posterior surface (circumvallate region) of the tongue. Sucrose, citric acid, sodium chloride and quinine hydrochloride were applied to the same areas to assess tastes responsiveness. On average, capsaicin and menthol produced "moderate" bitterness (and no other significant taste qualities) in the circumvallate region, and weaker bitterness on the side and tip of the tongue. Sensory irritation from capsaicin was rated significantly higher at the tongue tip, whereas menthol coolness was rated higher in the circumvallate region. In experiment 2 we applied sucrose and quinine hydrochloride together with capsaicin to investigate the effects other taste stimuli might have on capsaicin's reported bitterness. As expected, adding quinine produced stronger bitterness in the circumvallate and fungiform regions, and adding sucrose significantly reduced the bitterness of capsaicin in the circumvallate region. Overall, the results suggest that capsaicin and menthol are capable of stimulating a subset of taste neurons that respond to bitter substances, perhaps via receptor-gated ion channels like those recently found in capsaicin- and menthol-sensitive trigeminal ganglion neurons, and that the glossopharyngeal nerve may contain more such neurons than the chorda tympani nerve. That some people fail to perceive bitterness from capsaicin further implies that the incidence of capsaicin-sensitive taste neurons varies across people as well as between gustatory nerves.

Adolescent↗
PubMed1994

Use of mentholated cigarettes and oropharyngeal cancer.

We used data from a hospital-based case-control study of tobacco-related cancers to test the hypothesis that smoking mentholated cigarettes increases the risk of cancer of the oral cavity and pharynx, a cancer with a 50% higher incidence in black Americans compared with whites. Detailed information on smoking habits and other variables, obtained in personal interviews, was available for 194 male and 82 female newly diagnosed, histologically confirmed cases of oropharyngeal cancer and 845 male and 411 female controls, all of whom were current smokers. In univariate, stratified, and multivariable analyses involving all cases and controls, menthol was not a risk factor for cancer. The odds ratio, adjusted for covariates, for smoking mentholated cigarettes for > = 15 years relative to smoking nonmentholated cigarettes only was 0.9 (95% confidence interval = 0.5-1.6) in males, and 0.7 (95% confidence interval = 0.5-1.7) in females. In analyses by subsite, menthol use was positively associated only with cancer of the pharynx in males, although the magnitude of the association was small. These results indicate that use of mentholated cigarettes is unlikely to be an important independent factor in oropharyngeal cancer.

Aged↗
PubMed1994

Stimulation by menthol of Cl secretion via a Ca(2+)-dependent mechanism in canine airway epithelium.

1. To investigate the effect of menthol on airway epithelial ion transport function, we studied the bioelectrical properties of canine cultured tracheal epithelium by Ussing's short-circuit technique in vitro. 2. Addition of menthol (10(-3) M) to the mucosal but not the submucosal solution increased the short-circuit current (Isc) from 6.2 +/- 0.9 to 14.0 +/- 2.2 microA cm-2 (P < 0.001), and this effect was accompanied by increases in transepithelial potential difference and conductance. The response was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 6.4 +/- 0.9 microA cm-2 (P < 0.001) and 40 microM, respectively. 3. Other cyclic alcohols, including menthone and cyclohexanol, had no effect on the electrical properties. 4. The menthol-induced increase in Isc was not altered by pretreatment of the cells with amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate, furosemide or substitution of Cl with iodide in the medium. 5. Menthol (10(-3) M) increased cytosolic levels of free calcium ([Ca2+]i) from 98 +/- 12 to 340 +/- 49 nM (P < 0.01) in fura-2-loaded tracheal epithelium but did not affect the intracellular adenosine 3',5'-cyclic monophosphate content. 6. These results suggest that menthol stimulates Cl secretion across airway epithelium, probably through a Ca(2+)-dependent mechanism, and might thus influence mucociliary transport in the respiratory tract.

Animals↗
PubMed1995

Contact sensitivity to menthol and peppermint in patients with intra-oral symptoms.

We report 12 cases of contact sensitivity to the flavouring agents menthol and peppermint oil in patients presenting with intra-oral symptoms in association with burning mouth syndrome, recurrent oral ulceration or a lichenoid reaction. The patients were referred from the Glasgow Dental Hospital over a 4-year period for assessment of the possible contribution of contact sensitivity to their complaints. 5 patients with burning mouth syndrome demonstrated contact sensitivity to menthol and/or peppermint, with 1 patient sensitive to both agents, 3 positive to menthol only and 1 to peppermint only. 4 cases with recurrent intra-oral ulceration were sensitive to both menthol and peppermint. 3 patients with an oral lichenoid reaction were positive to menthol on patch testing, with 2 also sensitive to peppermint. 9 of the 12 cases demonstrated additional positive patch test results. After a mean follow-up of 32.7 months (range 9-48 months), of the 9 patients that could be contacted, 6 patients described clearance or improvement of their symptoms as a consequence of avoidance of menthol/peppermint.

Adult↗
PubMed1991

Effect of l-menthol on laryngeal receptors.

We have studied the effect of l-menthol on laryngeal receptors. Experiments have been conducted in 11 anesthetized dogs that breathed through a tracheostomy. We have recorded the activity of 23 laryngeal cold receptors and 19 mechanoreceptors. Constant flows of air, 15-50 ml/s (low) and 100-150 ml/s (high), passing for 10 s through the isolated upper airway in the expiratory direction, lowered laryngeal temperature and activated the cold receptors. This cold-induced discharge promptly ceased upon withdrawal of the airflow. Addition of l-menthol to the airflow evoked, for a similar decrease in temperature, a greater peak activation of the cold receptors than airflow alone (low flows 164%, high flows 111%); statistical significance was reached only for the lower flow. This activity outlasted the cessation of airflow by 30-120 s, even at a time when laryngeal temperature had returned to control (low flow 237%, high flow 307% of similar trials with airflow alone). Four laryngeal cold receptors were also tested with l-menthol added to a warm, humidified airflow that did not change laryngeal temperature; all of them were stimulated with a long-lasting discharge. Nine cold receptors were also tested with d-neomenthol and d-isomenthol; both isomers stimulated the receptors. None of the 19 mechano-receptors tested was affected by l-menthol. We conclude that l-menthol constitutes a specific stimulant of laryngeal cold receptors and could provide a useful tool for the study of their reflex effects.

Action Potentials↗
PubMed1992

Effect of l-menthol on the permeation of indomethacin, mannitol and cortisone through excised hairless mouse skin.

The effect of l-menthol on the skin permeability of mannitol, cortisone or indomethacin was examined by an in vitro penetration technique with hairless mouse skin. The donor solution was prepared with phosphate buffered saline, ethanol:buffered saline (20:80, v/v) or ethanol:buffered saline (20:80, v/v) containing 1% (w/v) l-menthol. Although ethanol showed little enhancing effect, l-menthol in an aqueous ethanol vehicle at pH 7.4 increased the permeability coefficients of mannitol and indomethacin by about 100 times that of the control (an aqueous vehicle) and increased that of cortisone by about 10 times. l-Menthol, however, scarcely enhanced the penetration of indomethacin at pH 3.0, the majority of the species being in unionized form. These results suggested that the menthol-ethanol-aqueous system enhanced skin permeability through a direct effect on the polar and/or lipid pathways, while the thermodynamic activity of the penetrant molecule in the delivery vehicle might also influence the effectiveness of the penetration enhancer.

Administration, Cutaneous↗
PubMed2004

Studies on the transdermal delivery of nimodipine from a menthol-based TTS in human volunteers.

The purpose of the present study was to design a membrane-moderated transdermal therapeutic system (TTS) of nimodipine using 2%w/w hydroxypropyl methylcellulose (HPMC) gel as a reservoir system containing menthol as penetration enhancer and 60%v/v ethanol-water as solvent system. The flux of nimodipine was markedly increased from 35.51 microg/cm2/h to 167.53+/-3.69 microg/cm2/h with the addition of 8%w/w menthol to HPMC drug reservoir. There was an increase in the flux of nimodipine through ethylene vinyl acetate (EVA) copolymer membrane with an increase in vinyl acetate content (9 to 28%w/w) of the copolymer. The permeability flux of nimodipine from the chosen EVA 2825 (with 28%w/w vinyl acetate content) was 152.05+/-2.68 microg/cm2/h, and this flux decreased to 132.69+/-1.45 microg/cm2/h on application of a water-based acrylic adhesive (TACKWHITE A 4MED) coat. However, the transdermal flux of nimodipine across EVA 2825 membrane coated with TACKWHITE A 4MED/ rat skin composite was found to be 116.05+/-2.39 microg/cm2/h, which is about 1.4 times greater than the required flux. Thus a new transdermal therapeutic system for nimodipine was designed using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED, and 2%w/w HPMC gel as reservoir containing 8%w/w of menthol as a penetration enhancer. The in vivo evaluation of nimodipine TTS patch was carried out to find the ability of the fabricated menthol-based TTS patch in providing the predetermined plasma concentration of the drug in human volunteers. The results showed that the menthol-based TTS patch of nimodipine provided steady plasma concentration of the drug with minimal fluctuations with improved bioavailability in comparison with the immediate release tablet dosage form.

Administration, Cutaneous↗
PubMed2002

[Kinetic study on the volatility of menthol and borneol].

OBJECTIVE: To study the volatile regularity of menthol and borneol in granule and lozenge at different temperature. METHOD: Kinetic method with GC being detection technique. RESULT: The volatility of menthol and borneol acts as a pseudo first-order reaction in open system. Under the same condition, the volatile rate of menthol and borneol in granule is four times as fast as that in lozenge, and the volatile rate of borneol is faster than that of menthol. CONCLUSION: This study can be applied to improve the quality of lozenges containing menthol or/and borneol.

Camphanes↗
PubMedDate not supplied

Effects of (-)-menthol on the distribution and metabolism of 2-aminofluorene in various tissues of Sprague-Dawley rats.

The purpose of the present study was to examine whether or not (-)-Menthol affects the distribution and metabolism of 2-aminofluorene (AF) in Sprague-Dawley rats. The AF, acetylated AF and AF metabolites were determined by using high performance liquid chromatography. AF was administered orally alone, with (-)-Menthol at the same time, and after 24-hour (-)-Menthol pretreatment and then urine, stool, blood and tissues from liver, kidneys, stomach, colon and bladder were collected and assayed for AF and its metabolites. Compared to the control group, (-)-Menthol caused an increase of the metabolites excreted in the urine and stool. The major metabolite excreted both in the urine and in the stool was 9-OH-AAF. The liver was the major metabolism center and the major residual metabolite of AF in the liver was 9-OH-AAF. When AF was given for 24 hours with (-)-Menthol to SD rats, the rate of carcinogen acetylation is decreased in bladder, blood, colon, kidney and liver tissues.

Administration, Oral↗