Association of Cold Receptor TRPM8 Gene Polymorphism with Blood Lipid Indices and Anthropometric Parameters in Shorians

Потапова, Т. А.; Yudin, N. A.; Pilipenko, I. V.; Kobsev, V. F.; Romashchenko, A. G.; Shakhtshneider, E.; Ogarkov, M. Yu.; Воевода, М. И.

doi:10.1007/s10517-011-1294-z

Cited by 6 publications

(3 citation statements)

References 11 publications

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“…The recent discovery of different receptors in the bladder, in subsets of sensory nerve fibres, responsive to temperature or molecules as capsaicin and menthol provides an opportunity to understand and treat TRPM8-related bladder painful disorders. For example, TRPM8 has been related to the painful or overactive bladder syndromes (OBS) ad painful bladder (PBS) or overreactive bladder syndromes 16 . PBS is a chronic bladder hypersensitivity disorder which causes suprapubic pain along with an increased micturition frequency and nocturia, while OBS is characterized by urinary urgency with or without urge incontinence and increased frequency 17 .…”

Section: Introductionmentioning

confidence: 99%

Novel selective, potent naphthyl TRPM8 antagonists identified through a combined ligand- and structure-based virtual screening approach

Beccari

Gemei

Monte

et al. 2017

Sci Rep

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Transient receptor potential melastatin 8 (TRPM8), a nonselective cation channel, is the predominant mammalian cold temperature thermosensor and it is activated by cold temperatures and cooling compounds, such as menthol and icilin. Because of its role in cold allodynia, cold hyperalgesia and painful syndromes TRPM8 antagonists are currently being pursued as potential therapeutic agents for the treatment of pain hypersensitivity. Recently TRPM8 has been found in subsets of bladder sensory nerve fibres, providing an opportunity to understand and treat chronic hypersensitivity. However, most of the known TRPM8 inhibitors lack selectivity, and only three selective compounds have reached clinical trials to date. Here, we applied two virtual screening strategies to find new, clinics suitable, TRPM8 inhibitors. This strategy enabled us to identify naphthyl derivatives as a novel class of potent and selective TRPM8 inhibitors. Further characterization of the pharmacologic properties of the most potent compound identified, compound 1, confirmed that it is a selective, competitive antagonist inhibitor of TRPM8. Compound 1 also proved itself active in a overreactive bladder model in vivo. Thus, the novel naphthyl derivative compound identified here could be optimized for clinical treatment of pain hypersensitivity in bladder disorders but also in different other pathologies.

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Section: Introductionmentioning

confidence: 99%

Novel selective, potent naphthyl TRPM8 antagonists identified through a combined ligand- and structure-based virtual screening approach

Beccari

Gemei

Monte

et al. 2017

Sci Rep

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“…41,43 This suggests that TRPM8 plays a role in multiple physiological processes beyond the detection of ambient cold and highlights the potential utility of targeting this receptor to produce favorable clinical outcomes. Despite this, and evidence that single nucleotide polymorphisms in the TRPM8 gene are associated with alterations in cholesterol and waist circumference, 82 the ability of MNTH to improve metabolic outcomes in humans remains unknown as MNTH has only been studied in human clinical trials to date for indications associated with pain (see clinical trial identifiers within). 83 Taken together, it seems warranted that future studies examine the clinical efficacy of MNTH for metabolic dysfunction and weight management.…”

Section: Discussionmentioning

confidence: 99%

Topical application of the pharmacological cold mimetic menthol stimulates brown adipose tissue thermogenesis through a TRPM8, UCP1, and norepinephrine dependent mechanism in mice housed at thermoneutrality

et al. 2022

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Increasing whole-body energy expenditure via the pharmacological activation of uncoupling protein 1 (UCP1)-dependent brown adipose tissue (BAT) thermogenesis is a promising weight management strategy, yet most therapeutics studied in rodents to date either induce compensatory increases in energy intake, have thermogenic effects that are confounded by sub-thermoneutral housing temperatures or are not well tolerated in humans. Here, we sought to determine whether the non-invasive topical application of the pharmacological cold mimetic and transient receptor potential (TRP) cation channel subfamily M member 8 (TRPM8) agonist L-menthol (MNTH), could be used to stimulate BAT thermogenesis and attenuate weight gain in mice housed at thermoneutrality. Using three different strains of mice and multiple complimentary approaches to quantify thermogenesis in vivo, coupled with ex vivo models to quantify direct thermogenic effects, we were able to convincingly demonstrate the following: (1) acute topical MNTH application induces BAT thermogenesis in a TRPM8-and UCP1-dependent manner; (2) MNTH-induced BAT thermogenesis is sufficient to attenuate weight gain over time without affecting energy intake in lean and obese mice; (3) the ability of topical MNTH application to stimulate BAT thermogenesis is mediated, in part, by a central mechanism involving the release of norepinephrine. These data collectively suggest that topical application of MNTH may be a promising weight management strategy.

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“…Moreover, the rs12472151 , rs11562975 , and rs28901637 polymorphisms of the TRPM8 gene were associated with metabolic syndrome, obesity, and cholesterol levels [ 138 , 139 , 140 ]. Variants at TRPM8, rs10166942 , and rs2362290 have been related to slower colonic transit rates, increased risk of irritable bowel syndrome, and chronic migraine [ 141 , 142 ].…”

Section: Pharmacogenomics Of Receptorsmentioning

confidence: 99%

Cannabis Pharmacogenomics: A Path to Personalized Medicine

Babayeva

Loewy

2023

CIMB

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Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and concerns regarding the cannabis/cannabinoid treatment and help us to understand the variability in individual responses and associated risks. Pharmacogenomics research has made meaningful progress in identifying genetic variations that play a critical role in interpatient variability in response to cannabis. This review classifies the current knowledge of pharmacogenomics associated with medical marijuana and related compounds and can assist in improving the outcomes of cannabinoid therapy and to minimize the adverse effects of cannabis use. Specific examples of pharmacogenomics informing pharmacotherapy as a path to personalized medicine are discussed.

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Association of Cold Receptor TRPM8 Gene Polymorphism with Blood Lipid Indices and Anthropometric Parameters in Shorians

Cited by 6 publications

References 11 publications

Novel selective, potent naphthyl TRPM8 antagonists identified through a combined ligand- and structure-based virtual screening approach

Novel selective, potent naphthyl TRPM8 antagonists identified through a combined ligand- and structure-based virtual screening approach

Topical application of the pharmacological cold mimetic menthol stimulates brown adipose tissue thermogenesis through a TRPM8, UCP1, and norepinephrine dependent mechanism in mice housed at thermoneutrality

Cannabis Pharmacogenomics: A Path to Personalized Medicine

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