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 55 records · Page 3Linked to original sources
PubMed1985

Menthol modulates oral sensations of warmth and cold.

Aqueous solutions of menthol were found to affect oral thermal sensation in the following ways: When menthol solutions were sipped and held in the mouth for 5 sec, solutions above oral temperature felt significantly warmer than deionized water of the same temperature (warmth enhancement). Menthol solutions below oral temperature felt cooler than water of the same temperature, but only slightly so (cold enhancement); Pretreating the mouth with 0.02% menthol for 5 min strengthened cold enhancement but attenuated sensations of warmth (warmth attenuation); Pretreating for 10 min produced continued cold enhancement while judgments of warmth returned to normal levels; L-menthol cooled more effectively than d-menthol, but d-menthol attenuated warmth at least as much as l-menthol. Possible explanations for the intermodal differences are discussed, and suggestions are made for future research into menthol's unexpectedly complex perceptual effects.

Adult↗
PubMed2004

Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol.

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, menthol did the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2mg/ml was administered easily to the anus and to remain at the administered site without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquid suppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhance the rectal bioavailability of ibuprofen.

Animals↗
PubMed1998

Penetration enhancement by menthol combined with a solubilization effect in a mixed solvent system.

The improvement in solubility of indomethacin due to the presence of menthol in various cosolvent systems consisting of water, alcohol and propylene glycol was examined by a mixture design in this study. A proper model to quantitatively describe the effect of menthol at different concentrations on the solubility of indomethacin was compared based on the statistical parameters provided by DESIGN-EXPERT. Then three cosolvent systems with the addition of menthol to solubilize indomethacin to extents of 1.0, 1.5 or 2.0% w/v were selected. The penetration of indomethacin through nude mouse skin from these three cosolvent systems with the addition of 0-12% menthol was investigated and followed by a discussion on the penetration mechanism. The results showed that menthol was able to improve drug solubility to different extents for different cosolvent systems. Optimally, a cosolvent system with an equal ratio of the three solvents, water, alcohol and propylene glycol, showed the highest extent of improvement in the solubility at all concentrations of menthol. The enhancement factors for indomethacin penetration due to menthol in different cosolvent systems were compared, based either on the permeation coefficient (Kp) or the separate overall effects on the skin (Flux). Both comparisons gave similar results. The influence of menthol was more significant compared to that of the cosolvent systems and the extent of this influence increased with an increase in the amount added, reaching a maximum at a specific amount of menthol for each different cosolvent system.

Animals↗
PubMed2000

Whisker growth of l-menthol in coexistence with various excipients.

The purpose of the present study was to clarify the mechanism for l-menthol whisker growth. l-Menthol was mixed with an excipient, and the interaction was examined by IR measurement, thermal analysis and powder X-ray diffraction. Then we examined the involvement of the capillary condensation using the pore size distribution measurement. By mixing l-menthol with an excipient with whisker growth, the hydroxyl group stretching band of l-menthol was shifted to the higher wavenumber in the IR spectrum, the melting point and heat of fusion of l-menthol became lower in the thermal analysis, and the diffraction intensity of l-menthol became lower in the powder X-ray diffraction. The excipients with whisker growth showed the tendency to have the meso-pore involved in the capillary condensation in the pore size distribution measurement. From the above results, the whisker growth mechanism is considered as follows. When l-menthol was mixed with an excipient with whisker growth, the crystallinity of l-menthol was lowered and the vapor pressure was increased by the interaction mainly consisting of the hydrogen bond. The generated l-menthol vapor entered meso-pore, the saturated vapor pressure was lowered by the capillary condensation, and the nucleation occurred. The vapor was further supplied, generating the growth of whisker.

Crystallization↗
PubMed2006

High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol.

Menthol is a cooling compound derived from mint leaves and is extensively used as a flavoring chemical. Menthol activates transient receptor potential melastatin 8 (TRPM8), an ion channel also activated by cold, voltage and phosphatidylinositol-4,5-bisphosphate (PIP2). Here we investigated the mechanism by which menthol activates mouse TRPM8. Using a new high-throughput approach, we screened a random mutant library consisting of approximately 14,000 individual TRPM8 mutants for clones that are affected in their response to menthol while retaining channel function. We identified determinants of menthol sensitivity in two regions: putative transmembrane segment 2 (S2) and the C-terminal TRP domain. Analysis of these mutants indicated that activation by menthol involves a gating mechanism distinct and separable from gating by cold, voltage or PIP2. Notably, TRP domain mutations mainly attenuated menthol efficacy, suggesting that this domain influences events downstream of initial binding. In contrast, S2 mutations strongly shifted the concentration dependence of menthol activation, raising the possibility that S2 influences menthol binding.

Amino Acid Sequence↗
PubMed2006

The inhibition of bone resorption in rats treated with (-)-menthol is due to its metabolites.

(-)-Menthol, a monoterpene from Mentha species (Lamiaceae), has been shown to inhibit bone resorption in vivo by an unknown mechanism. In the present study, plasma and urine profiling in rats determined by GC/MS demonstrate that (-)-menthol is extensively metabolized, mainly by hydroxylation and carboxylation, and excreted in the urine, in part as glucuronides. In plasma, very low concentrations of (-)-menthol metabolites were detected after a single dose of (-)-menthol, whereas after repeated treatment, several times higher concentrations and long residence times were measured. In contrast, the elimination of unchanged (-)-menthol was increased by repeated treatment. (-)-Menthol, at concentrations found in plasma, did not inhibit bone resorption in cultured mouse calvaria (skull). However, the neutral metabolites of (-)-menthol, extracted from urine of rats fed with (-)-menthol, inhibited bone resorption in vitro, the concentrations being at plasma level or higher. These results suggest that not (-)-menthol itself, but one or several of its neutral metabolites inhibit the bone resorbing cells in vivo.

Administration, Oral↗
PubMedDate not supplied

Determination of encapsulated menthol flavour using thermal desorption gas chromatography.

The analysis of menthol in encapsulated products is challenging due to the nature of the encapsulating matrices and the volatility of the analyte. Normal sampling/extraction procedures cannot be applied to the different types of menthol encapsulated products, due to variable extraction efficiencies of the analyte. This paper details the extraction and analysis of menthol flavour using a two stage thermal desorption GC process. This two stage thermal desorption system, using a Tenax TR packed cold trap, enables a narrow band of the extracted menthol to be focused onto the GC column. The method showed linearity in the range of 0.2-0.8 mg of menthol with a correlation coefficient greater than 0.999. Average instrumental precision of 3% RSD was determined and method precision was in the range of 2.1-9.4% RSD. This method was specific to menthol showing no interfering peaks. All the menthol was extracted in one extraction step. The specific analysis of menthol in encapsulated products allowed comparison of the efficiency of encapsulating processes, by comparing menthol loading values. RSD values for the different microparticles also indicate the relative homogeneity of the systems.

Calibration↗
PubMed2004

Physiological, psychological, social, and cultural influences on the use of menthol cigarettes among Blacks and Hispanics.

Patterns of menthol cigarette consumption among Blacks and Hispanics are likely a product of the interactive effects of several factors: the physiological and pharmacological sensory effects of menthol, the "cool" psychological identity of being menthol smokers, the promotional marketing of menthol cigarettes, and the cultural effects of health-related beliefs and subjective culture norms. This article presents two conceptual frameworks--a moderation logic model and a mediation logic model--for organizing the disparate literature on factors affecting the consumption of menthol cigarettes among Blacks and Hispanics. Three factor domains are examined as direct effect predictors of menthol cigarette smoking: (a) physiological and pharmacological, (b) psychological, and (c) social and environmental. In addition, a fourth domain of cultural variables is presented as a class of moderator or mediator variables that can interact with these physiological, psychological, and social factors as determinants of menthol cigarette use. These cultural variables are examined as mediating or moderating factors that influence the use of menthol cigarettes by Black and Hispanic consumers. Recommendations are offered for future research to further understand the influence of cultural and other factors as determinants of menthol cigarette smoking among Blacks and Hispanics.

Attitude to Health↗
PubMed2004

Application, function, and effects of menthol in cigarettes: a survey of tobacco industry documents.

Menthol cigarettes are the only cigarette market category identified by use of a flavor additive and constitute more than a quarter of the overall market. Menthol also is used at reduced levels in many nonmenthol brands. Public health research has suggested patterns of use of mentholated brands as a potential explanation for the health disparities between Black (largely menthol) and White (largely nonmenthol) smokers and has explored the effects of menthol on smoker behavior, consumption patterns, and consequent delivery of smoke constituents. However, relatively few published studies have directly examined the physiological impact and function of menthol delivery in cigarettes. In this study, we review internal tobacco industry documents to assess industry research on function and effects of menthol in cigarettes. Industry documents describe a range of physiological effects of menthol, with important implications for use and consumption patterns. These effects include altered perception of tobacco smoke and its constituents via cooling, smoothing, and anesthetic effects; increased impact through stimulation of trigeminal receptors; interaction with nicotine controlling its perception, delivery, and uptake; and increased respiratory irritation and toxic effects. Further studies are needed to evaluate these findings. We conclude that the unique differences between menthol cigarettes and nonmenthol cigarettes must be considered in research, cessation treatment, and enactment of tobacco product regulations.

Central Nervous System↗
PubMed2004

Adolescent menthol smokers: will they be a harder target for cessation?

Menthol smoking may influence the development of tobacco addiction and related health consequences, yet limited data on menthol smoking by youth are available. We assessed usual brand menthol preference by Baltimore-area teenage smokers applying to a smoking cessation study between September 1999 and December 2002. Of a biethnic (Black and White) sample of 593 youths (mean age=15.5+/-1.4 years, 51% female, 45% African American), the overwhelming majority (93%) were menthol smokers. Menthol preference rates were highest among African American girls and lowest among White boys. Overall, a statistically significant association was found between ethnicity and menthol preference, chi2 (df=1)=19.4, p<.001. This association also was observed separately for girls, chi2 (df=1)=9.21, p=.0024, and for boys, chi2 (df=1)=9.59, p=.0020. Menthol smoking did not vary with age in either ethnic group. These findings of overwhelming menthol preference in a treatment-seeking sample of adolescents warrant further research on the developmental trajectory, cessation, and health-related impact of menthol smoking by youth.

Administration, Inhalation↗
PubMed2004

Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors.

Although cold hyperalgesia is a frequent symptom in patients with neuropathic pain, it is poorly understood. We investigated the mechanisms of cold pain by studying the effect of menthol on pain, temperature perception, touch sensation and skin perfusion. In 10 subjects, 40% l-menthol, and ethanol, serving as control, were topically applied to the forearm in a double-blinded two-way crossover study. Menthol induced significant pain and cold sensations, punctate and cold hyperalgesia and an increase in cutaneous perfusion. Other mechano-sensory and thermal tests were unchanged (touch, cold and warm detection thresholds, heat pain threshold; no dynamic and static hyperalgesia, no wind-up). To investigate the underlying mechanisms, the effects of menthol versus ethanol on the dorsum of the hand were tested during A fibre conduction blockade of the superficial radial nerve in another 10 subjects. The block itself led to hypoaesthesia for mechanical stimuli and anaesthesia for cold perception, but induced an increase in cold-mediated pain. This was due to lack of inhibition of C nociceptors normally exerted by concomitant activation of A fibres. Under these conditions, menthol-induced cold sensation and punctate hyperalgesia were abolished. However, menthol induced spontaneous pain with a trend to higher values than without block. Furthermore, the hyperalgesia to cold stimuli, that was already present during A fibre block, was further increased significantly by menthol. We suggested that menthol acts to sensitize cold-sensitive peripheral vasoactive C nociceptors and activates cold-specific A delta fibres. Punctate hyperalgesia is due to central sensitization based on the ongoing activity in the sensitized cold-sensitive peripheral C nociceptors. In conclusion, topical menthol is a human model for cold pain by exposing for the first time the mechanism of sensitized peripheral cold C nociceptors that may also be involved in neuropathic pain.

Administration, Topical↗
PubMed2001

Effects of (-)-menthol on arylamine N-acetyltransferase activity in human liver tumor cells.

To evaluate whether or not (-)-menthol affects arylamine N-acetyltransferase (NAT) activity, we selected human liver tumor cell line (J 5) for examination. By using high performance liquid chromatography, NAT activity for acetylation of 2-aminofluorene (AF) was determined. (-)-Menthol displayed a dose-dependent inhibition to cytosolic NAT activity. Time-course experiments showed that NAT activity measured from intact human liver tumor cells was inhibited by (-)-menthol for up to 24 hrs. But in human liver tumor intact cells, the low doses (0.0032 and 0.032 mM) of (-)-menthol promoted the NAT activity and the high doses (3.2 and 32 mM) of (-)-menthol inhibited NAT activity and the 0.32 mM (-)-menthol did not show any significant differences between control and (-)-menthol treated groups. Using standard steady-state kinetic analysis, it was demonstrated that (-)-menthol was a possible uncompetitive inhibitor (decrease Km and Vmax) to NAT activity in cytosols. This report is the first demonstration which showed (-)-menthol affect on human liver tumor cells NAT activity.

Antineoplastic Agents↗
PubMed2006

Neurons in superficial trigeminal subnucleus caudalis responsive to oral cooling, menthol, and other irritant stimuli.

The recent discoveries of cold-sensitive transient receptor potential (TRP) channels prompted us to investigate the responses of neurons in trigeminal subnucleus caudalis (Vc) to intraoral cooling and agonists of TRPM8 and TRPA1. Single units responsive to lingual cooling were recorded in superficial laminae of Vc in thiopental-anesthetized rats. All units responded to noxious heat and 88% responded to menthol. Responses increased with menthol concentration from 0.1 to 1% (6.4-64 mM) and plateaued at 10% (640 mM). Noxious cold-evoked responses were significantly enhanced after menthol in a concentration-dependent manner. Constant-flow application of 1% menthol elicited a phasic discharge that adapted over 2-8 min and significantly enhanced subsequent cold-evoked but not heat-evoked responses; vehicle (10% ethanol) was ineffective. Reapplication of menthol 15 min later elicited a significantly reduced response (self-desensitization). Vc units were similarly excited phasically by 1% menthol dissolved in 40% ethanol. The 40% ethanol briefly excited Vc units during the first minute and reduced subsequent responses to noxious heat and cold while exhibiting neither self-desensitization nor cross-desensitization to menthol. Menthol cross-desensitized Vc responses to 40% ethanol. Most menthol-responsive units also responded to the TRPA1 agonists cinnamaldehyde and mustard oil, and the TRPV1 agonist capsaicin. Units in superficial Vc receive convergent input from primary afferents that express TRPM8, TRPA1, and/or TRPV1 channels, either directly or indirectly via intersubnuclear pathways. The convergent nature of these units suggests a general role in signaling noxious stimuli.

Animals↗
PubMed1996

Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin.

The effect of menthol and alcohol as its vehicle on thermal sensations, pain, experimental itch and irritation were studied in 18 subjects, using a computerized thermal sensory analyzer, laser Doppler flowmetry and an evaporimeter for transepidermal water loss (TEWL). Menthol had a subjective cooling effect lasting up to 70 min in 12/18 subjects; however, it did not affect cold and heat threshold, nor did it affect cold and heat pain threshold. Alcohol produced an immediate cold sensation lasting up to 5 min in 4/18 subjects and lowered the sensitivity of cold sensation threshold (P < 0.05). Histamine injection did not change thermal and pain thresholds. Menthol did not alleviate histamine-induced itch magnitude, nor its duration. Following histamine injection, cold sensation median threshold decreased by 1.2 degrees C from (29.9 degrees C to 28.7 degrees C) on the site treated with menthol (P < 0.01) with similar changes in thresholds at the alcohol-treated site (P < 0.05). Warm sensation and pain threshold in subjects receiving histamine injections, measured after menthol and alcohol application, did not differ from their baseline values with histamine alone. TEWL at the site treated with menthol was significantly higher (P < 0.05) than at the alcohol-treated and the control site (P < 0.01), suggesting that menthol has a higher skin irritating effect, or at least alters the stratum corneum water permeability. Our results suggest that menthol fulfills the definition of a counterirritant, but does not affect histamine-induced itch, nor does it affect pain sensation.

Administration, Topical↗
PubMed2003

Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers.

OBJECTIVES: The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people. METHODS: Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study. RESULTS: Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments. CONCLUSIONS: We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.

Administration, Oral↗
PubMed1993

Taste prestimulation increases the chorda tympani nerve response to menthol.

Electrophysiological recordings of the summated response of the chorda tympani nerve to menthol stimulation of the tongue were obtained from 15 adult Sprague-Dawley rats. The chorda tympani nerve response to menthol was of short duration, ending within 2.5 s after stimulus onset, leaving the receptors in a state of insensitivity to subsequent menthol stimulation. Rinse durations with deionized-distilled water up to 10 min failed to bring the receptors back to their original prestimulus state. Although stimulation with menthol prevented taste receptors from responding to subsequent presentations of menthol, the chorda tympani nerve would respond normally to NaCl, NH4Cl, KCl, sodium acetate, glucose, citric acid, and quinine-HCl solutions. Prior stimulation with one of these taste solutions resulted in the recovery of the menthol response. The magnitude of the recovered menthol response depended on the magnitude of the phasic response elicited by the preceding taste stimulus. A general explanation involving possible reception and transduction mechanisms was offered to account for menthol's unexpected stimulatory effects on the chorda tympani nerve.

Animals↗
PubMed2004

Role of mentholated cigarettes in increased nicotine dependence and greater risk of tobacco-attributable disease.

BACKGROUND: Cold air stimulates upper airway cold receptors causing a reflex depressive effect on respiratory activity. Menthol, in low concentrations can also stimulate these same cold receptors causing a depressive effect on respiratory activity. Menthol cigarettes when smoked, deliver enough menthol to stimulate cold receptors resulting in the smoker experiencing a "cool sensation." The "cool sensation" experienced by the menthol smoker can result in a reflex-depressive effect on respiratory activity. METHOD: Literature searches were done for the NLM databases (e.g., MEDLINE from 1966, TOXLINE, OLDMEDLINE (1985-1965), CANCERLIT, plus tobacco industry documents and hardcopy indices. The evidence was evaluated with application to mentholated cigarette smoking. RESULTS AND DISCUSSION: A logical progression is presented that develops the framework to prove that menthol found in mentholated cigarettes may cause respiratory depression resulting in greater exposure to the toxic substances found in tobacco smoke. CONCLUSION: As a result of breath holding that results from the stimulation of cold receptors there is a greater opportunity for exposure and transfer of the contents of the lungs to the pulmonary circulation. For the menthol smoker this results in a greater exposure to nicotine and the particulate matter (tar) of the smoked cigarette. This exposure can result in increased nicotine dependence and greater chance of tobacco-attributable disease.

Black or African American↗
PubMed2003

Comparison of skin permeation enhancement by 3-l-menthoxypropane-1,2-diol and l-menthol: the permeation of indomethacin and antipyrine through Yucatan micropig skin and changes in infrared spectra and X-ray diffraction patterns of stratum corneum.

3-l-Menthoxypropane-1,2-diol (MPD) is a derivative of l-menthol, which has an enhancement effect on drug permeation through skin. In this study, the effect of MPD on drug permeation through skin was compared with that of l-menthol. MPD or l-menthol at final concentrations of 3% in 40% ethanol was added to the drugs indomethacin or antipyrine and each mix then applied to Yucatan micropig skin in vitro. Drug concentrations in the skin were higher in the presence of either MPD or l-menthol, however, only l-menthol shortened the lag time of permeation. MPD enhanced the skin permeation of the drugs only by increasing the skin concentration of the drugs. In contrast, l-menthol enhanced the skin permeation of the drugs by increasing both the skin concentration and the diffusion rate in skin. The infrared (IR) spectra and X-ray diffraction patterns of stratum corneum after treatment with MPD did not differ from those of intact stratum corneum. A change in the IR spectra of stratum corneum after treatment with l-menthol was observed at the CH band, and the peaks representative of the lipid structure in the X-ray diffraction patterns decreased in intensity. These results suggest that l-menthol, but not MPD, disrupts the intercellular lipid structure of stratum corneum. Thus, MPD is expected to be a moderate skin permeation enhancer.

Administration, Topical↗