Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of menthol and peppermint oil were determined in guinea-pig ileal smooth muscle, in rat and guinea-pig atrial and papillary muscle, in rat brain synaptosomes and in chick retinal neurones by pharmacological 45Ca2+ uptake and radioligand binding assays. Menthol is a major constituent of peppermint oil and is approximately twice as potent as peppermint oil as an inhibitor of K+ depolarization-induced and electrically stimulated responses in ileum and electrically stimulated atrial and papillary muscles. IC50 values in the ileal preparation ranged from 7.7 to 28.1 micrograms ml-1 and in the cardiac preparations from 10.1 to 68.5 micrograms ml-1. Similar potencies were demonstrated against K+ depolarization-induced 45Ca2+ uptake in synaptosomes and against K+ depolarization and Bay K 8644-induced uptake in chick retinal neurons. IC50 values for menthol inhibition of K+ and Bay K 8644 responses in the retinal neurons were 1.1 x 10(-4) M (17.2 micrograms ml-1) and 1.75 x 10(-4) M (26.6 micrograms ml-1), respectively, and for peppermint oil were 20.3 and 41.7 micrograms ml-1 respectively. Both menthol and peppermint oil inhibited specific [3H]nitrendipine and [3H]PN 200-110 binding to smooth and cardiac muscle and neuronal preparations with potencies comparable to, but slightly lower than, those measured in the pharmacological and 45Ca2+ uptake experiments. Binding of menthol and peppermint oil, studied at 78 micrograms ml-1, was competitive against [3H]nitrendipine in both smooth muscle and synaptosome preparations. The data indicate that both menthol and peppermint oil exert Ca2+ channel blocking properties which may underlie their use in irritable bowel syndrome. Ca2+ channel antagonism may not be the only pharmacological effect of menthol and peppermint oil contributing to intestinal smooth muscle relaxation.
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PMID:The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations. 285 2

Menthol-beta-D-glucuronide is a potential prodrug for colonic delivery of the spasmolytic agent menthol. Menthol is the primary constituent of peppermint oil, which is used to treat the irritable bowel syndrome. The chemical stability of menthol-beta-D-glucuronide was assessed at various pHs (1.5, 4.5, 6.0 and 7.4) over a 4 to 24 h period at 37 degrees C. The prodrug was stable, i.e., there was less than 0.1% hydrolysis of the prodrug, at pHs of 4.5, 6.0 and 7.4. At pH 1.5, the prodrug was about 20% hydrolyzed over a 4 h period suggesting the need for an enteric coating to prevent premature hydrolysis in the stomach. The stability of the prodrug was also assessed in luminal contents of the laboratory rat and in human stool samples. These studies were performed at concentrations designed to assess relative velocities of hydrolysis (i.e., substrate concentrations in excess of the Km). The prodrug was stable in luminal contents of the rat stomach, proximal small intestine, and the distal small intestine. The rate of hydrolysis of menthol-beta-D-glucuronide was 6.26 +/- 2.88 nmol min-1 mg-1 and 2.34 +/- 1.22 nmol min-1 mg-1 in luminal contents of the rat cecum and colon, respectively. The hydrolysis rate of menthol-beta-D-glucuronide was lower in human stool samples (0.52 +/- 0.46 nmol min-1 mg-1). The prodrug had a measured log octanol/buffer partition coefficient of -1.61 suggesting it should be poorly absorbed from the lumen of the gastrointestinal tract. The data support the hypothesis that menthol-beta-D-glucuronide is a candidate for the delivery of menthol to the large intestine under in vivo conditions.
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PMID:Menthol-beta-D-glucuronide: a potential prodrug for treatment of the irritable bowel syndrome. 789 32

Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in the production of other compounds. Various extracts from peppermint contain menthol as a major active constituent and have been used for centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome as well as an insect repellent. Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. Notwithstanding its plethora of benefits, menthol's coldsensitivity response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in mentholated cigarette brands thus potentially leading to toxic effects. Menthol may prove a valuable lead structure for the synthesis of drugs that target multiple receptors involved with a number of pharmacological effects.
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PMID:Menthol--pharmacology of an important naturally medicinal "cool". 2306 35

Menthol, a monoterpene, is a principal component of peppermint oil and is used extensively in consumer products as a flavoring aid. It is also commonly used medicinally as a topical skin coolant; to treat inflammation of the mucous membranes, digestive problems, and irritable bowel syndrome (IBS); and in preventing spasms during endoscopy and for its spasmolytic effect on the smooth muscle of the gastrointestinal tract. Menthol has a half life of 3-6 h and is rapidly metabolized to menthol glucuronide which is detectable in urine and serum following menthol use. We describe a method for the determination of total menthol in human plasma and urine using liquid/liquid extraction, gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring mode and menthol-d4 as the internal standard. Controls are prepared with menthol glucuronide and all samples undergo enzymatic hydrolysis for the quantification of total menthol. The method has a linear range of 5-1000 ng/mL, and coefficient of variation <10%.
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PMID:Determination of Menthol in Plasma and Urine by Gas Chromatography/Mass Spectrometry (GC/MS). 2666 Jan 89