Menthol Subject

Pure piperitone was subjected to the action of purified hydrogen, in the presence of a nickel catalyst, for six hours, the temperature ranging between 175° to 180° C. The double bond in piperitone was readily opened out with the formation of menthone, but further action of the hydrogen under these conditions did not reduce the carbonyl group, even after continued treatment for two days. Under correct conditions, however, the reduction to menthol should take place. The ease with which menthone is formed in this way is of special interest, not only in connection with the production of this ketone, but also as a stage in the manufacture of menthol. 

An interaction between main olfaction and the trigeminal somatosensory system has been proposed to facilitate directional smelling. For carbon dioxide and menthol, human subjects were able to tell the odor direction in 96% of cases, while the results for hydrogen sulfide and vanillin were random (Kobal et ah, 1989). Rats can discriminate odor direction in one sniff (Rajan et ah, 2006). 

The synthesis of racemic Tic (rac-33) can be accomplished by alkylation of acet-amidomalonates in a reasonable yield (Scheme 15). Racemic Tic can then be subjected to resolution using menthol.1[7 ] This route is a good alternative for synthesizing both enantiomers of Tic. 

Menthol is a compound that contains C, H and O. It is derived from peppermint oil and is used in cough drops and chest rubs. When 0.2393 g of menthol is subjected to carbon-hydrogen combustion analysis, 0.6735 g of C02 and 0.2760 g of H20 are obtained. 

Actinomycetes, primarily streptomycetes, are capable of producing highly odorous volatile metabolites in low yields in submerged culture. This subject has been reviewed in detail(37). Among the more important volatiles identified ares geosmin, the earthy odor, methyl isoborneol, having a camphor or menthol odor 2-methoxy-3-isopropyl pyrazine, with a musty vegetable odor and miscellaneous compounds such as sesquiterpenoids and lactones. 

Menthol (Ji = 156.3 g/mol), a strong-smelling substance used in cough drops, is a compound of carbon, hydrogen, and oxygen. When 0.1595 g of menthol was subjected to combustion analysis, it produced 0.449 g of CO2 and 0.184 g of H2O. What is menthol s molecular formula ... 

Morice AH, Marshall AE et al (1994) Effect of inhaled menthol on citric acid induced cough in normal subjects. Thorax 49 1024-1026... 

Morice AH, Marshall AE, Higgins KS, Grattan TJ (1994) Effect of inhaled menthol on citric acid induced cough in normal subjects. Thorax 49 1024-1026 Morice AH, Kastehk JA, Thompson R (2001) Cough challenge in the assessment of cough reflex. Br J Chn Pharmacol 52 365-375... 

In healthy subjects, menthol vapor inhibits citric acid induced cough, unlike other aromatic oils which were used to act as placebos (Packman and London 1980 Morice et al. 1994). Unfortunately no properly designed clinical trials of vaporized menthol against cough seem to have been done, possibly for lack of an adequate placebo, but the basic studies suggest that it is potentially an active antitussive. 

A crossover study in 11 healthy subjects found that a single 100-mg dose of menthol taken with coffee containing 200 mg caffeine increased the time to maximum caffeine concentration by about 30 minutes. The increase in the actual maximum concentration was not significant, and there were no significant effects on caffeine half-life. It was thought that menthol reduced the rate of caf-... 

In the last 25 years or so, this subject has occupied more organic chemists than possibly any other, and we are now at a point where it is not only possible (and in fact essential because of strict regulatory rules) to make many drug molecules as single enantiomers, but it is also even possible to make many chiral molecules that are indigenous to nature more cheaply in the laboratory. By 2007, for example, at least 30% of the world s supply of menthol was not extracted from plants but made synthetically. A thousand tonnes of (-)-menthol a year is made by the company Takasago in Japan using the techniques of asymmetric synthesis that you will meet later in this chapter. 

A study was conducted which did not employ a frequency symmetric experiment prior to direct covariance processing. Zhang et al. [80] subjected a 2D C—C INADEQUATE data set of 2048 x 1024 data points to covariance NMR. They thus transformed the common double-quantum representation of an INADEQUATE spectrum into a symmetric singlequantum map. The resulting symmetric spectrum was considered easier to interpret. Menthol 2 was used as reference compound. 

In 20 healthy volunteers subjected to menthol-evoked cold pain tramadol 100 mg significantly reduced hyperalgesia and was associated with minor adverse reactions, mainly nausea and fatigue, with an NNTh of 1.6 (95% Cl = 1.16, 2.79) [187. ... 

A second study used the same essential oUs when investigating the skin perfusion of the head in healthy subjects and migraine patients. In the former, capUlary ow was increased by 225% in comparison to baseline by peppermint oil, while eucalyptus decreased the ow by 16%. In migraine patients, neither essential oil had any effect. It was suggested that the absence of capUlary vaso dilation (normally caused by menthol) was due to impaired calcium channel function in migraine patients (Gobel et al., 1995b). 

Various over-the-counter preparations containing methyl salicylate and menthol have been used to treat musculoskeletal pain for many years, but few have been the subjects of clinical trials. Menthol is class ed as a counterirritant, producing a cooling sensation via activation of sped c thermoreceptors (Patel et al., 2007), while methyl salicylate has analgesic, anti-in ammatory, and vasodila-tory effects (Green and Flammer, 1989). 

Despite being used as a component in cough remedies since the introduction of a VapoRub in 1890, there are few human trials of menthol used alone as being effective. In a citric acid-induced cough model in healthy subjects. Packman and London (1980) found that menthol was effective, although 1,8-cineole was more ef cacious. The use of an aromatic unction rather than direct inhalation may have affected the results, since the inhalation of menthol has been shown in animal models to be signi cantly more effective at cough frequency reduction (28% and 56% at 10 and 30 pg/L, respectively) when compared to 1,8-cineole (Laude et al., 1994). 

In a double-blind, randomized trial, subjects suffering from the common cold were given lozenges containing 11 mg of menthol. Posterior rhinomanometry could detect no change in nasal resistance to air ow after 10 min however, there were signi cant changes in the nasal sensation of air ow (Eccles et al, 1990). 

Thus, it has been demonstrated that menthol is not a nasal decongestant. However, it is useful in therapy since stimulation of the cold receptors causes a subjective sensation of nasal decongestion and so relieves the feeling of a blocked nose. In commercial preparations that include menthol, a true decongestant such as oxymetazoline hydrochloride is often present. 

Recent in vitro studies have shown that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of these receptors by cold and menthol excite these airway autonomic nerves. Thus, activation of TRPM8 receptors may provoke an autonomic nerve re ex to increase airway resistance. It was postulated that this autonomic response could provoke menthol- or cold-induced exacerbation of asthma and other pulmonary disorders (Xing et al, 2008). Direct cold stimulation or inhalation of menthol can cause immediate airway constriction and asthma in some people perhaps, the TRPM8 receptor expression is up regulated in these subjects. The situation is far from clear. 

By the measurement of lung and forced expiratory volumes, nasal, lower and total airway resistances, closing volume data, the phase III slope of the alveolar plateau, and the maximum expiratory ow volume, peripheral airway dysfunction was con rmed in 24 adults with common colds. In a randomized, controlled trial, an aromatic mixture of menthol, eucalyptus oil, and camphor (56%, 9%, and 35% w/w, respectively) were vaporized in a room where the subjects were seated. Respiratory function measurements were made at baseline, 20 and 60 min after exposure. After the last measurement, phenylephrine was sprayed into the nostrils and the measurements taken again 5-10 min later to determine potential airway responsiveness. The control consisted of tap water. The results showed sign cant changes in forced vital capacity, forced expiratory volume, closing capacity, and the phase III slope after aromatic therapy as compared to the control. It was con eluded that the aromatic inhalation favorably modi ed the peripheral airway dysfunction (Cohen and Dressier, 1982). 

In a randomized, placebo controlled trial of citric acid-induced cough in 20 healthy subjects, the inhalation of a combination of menthol and eucalyptus oil (75% and 25%, respectively) signi cantly decreased the cough frequency (Morice et al., 1994). 

Eccles, R., Jawad, M. S., Morris, S. 1990. The effects of oral administration of (-) -menthol on nasal resistance to air ow and nasal sensation of air ow in subjects suffering from nasal congestion associated with the common cold../. Pharm.. Pharmacol. 42 652-654. 

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