1-Methylnicotinamide

Ion 1-Methylnicotinamide.svg 150px 3-Carbamoyl-1-methylpyridin-1-ium Trigonellamide; N1-Methylnicotinamide; NMN 3106-60-3 1005-24-9(chloride) 16797 71733 444 DB11710 C02918 457 UM47085BXC 1S/C7H8N2O/c1-9-4-2-3-6(5-9)7(8)10/h2-5H,1H3,(H-,8,10)/p+1 LDHMAVIPBRSVRG-UHFFFAOYSA-O C[N+]1=CC=CC(=C1)C(=O)N 7 9 2 1 + 1-Methylnicotinamide (1-MNA, trigonellamide) is a prototypic organic cation.Sokol, P. P. Holohan, P. D. Ross, C. R. 1986 Essential disulfide and sulfhydryl groups for organic cation transport in renal brush-border membranes https://www.jbc.org/article/S0021-9258(17)35779-4/pdf Journal of Biological Chemistry 261 7 3282–3287 10.1016/S0021-9258(17)35779-4 2936734 free 5 March 2021 1-Methylnicotinamide is the methylated amide of nicotinic acid (vitamin B3). 1-Methylnicotinamide is an endogenic substance that is produced in the liver when nicotinamide is metabolized. It is a typical substance secreted in the kidney. It participates in the nicotinamide salvage pathway within the NAD+ (nicotinamide adenine dinucleotide) metabolic pathway, thereby contributing to optimizing NAD+ levels.Li Jing-Jing Sun Wei-Dong Zhu Xiao-Juan Mei Ya-Zhong Li Wen-Song Li Jiang-Hua 2024-06-19 Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions Metabolites en 14 6 343 10.3390/metabo14060343 2218-1989 11205546 38921477 free Occurrence To date, the highest natural concentration of 1-methylnicotinamide has been found in the alga Undaria pinnatifida (3.2 mg/100 g of dried algae) and green tea leaves (3 mg/100 g of product). Other products with notable 1-MNA content include celery (1.6 mg/100 g of product), Chinese black mushrooms (shiitake, 1.3 mg/100 g), and fermented soybeans (natto, 1.0 mg/100 g).Taguchi H. Sakaguchi M. Shimabayashi Y. 1986 ja:各種食品中のキノリン酸,トリゴネリンおよびN1-メチルニコチンアミドの含量ならびに加熱によるそれらのニコチン酸,ニコチンアミドへの変換 Contents of quinolinic acid, trigonelline and N1-methylnicotinamide in various foods and thermal conversion of these compounds into nicotinic acid and nicotinamide ビタミン ja 60 11 537–546 10.20632/vso.60.11_537 ja:ビタミン Vitamins Biosynthesis 1-Methylnicotinamide can be produced in the liver by nicotinamide N-methyltransferase (NNMT). The reaction takes place during the metabolism of NAD+ (nicotinamide adenine dinucleotide). NNMT is also present in brain tissue, adipose tissue, muscle tissue, kidneys, and skin.GTEx Portal https://www.gtexportal.org/home/index.html 2024-12-06 www.gtexportal.org NNMT (nicotinamide N-methyltransferase) is an enzyme that in humans is encoded by the NNMT gene.Aksoy S, Brandriff BF, Ward A, Little PF, Weinshilboum RM Mar 1996 Human nicotinamide N-methyltransferase gene: molecular cloning, structural characterization and chromosomal localization Genomics 29 3 555–561 10.1006/geno.1995.9966 8575745 NNMT catalyzes the methylation of nicotinamide and similar compounds using the methyl donor S-adenosyl methionine (SAM-e) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide.Pissios P 2017 Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme Trends in Endocrinology and Metabolism 28 5 340–353 10.1016/j.tem.2017.02.004 5446048 28291578 NNMT is highly expressed in the human liver. Role in the body Scientific research highlights numerous therapeutic and health-promoting properties of 1-MNA, including vascular protective,Bartuś M. Łomnicka M. Kostogrys R. B. Kaźmierczak P. Watała C. Słominska E. M. Smoleński R. T. Pisulewski P. M. Adamus J. Gębicki J. Chlopicki S. 2008 1-Methylnicotinamide (MNA) prevents endothelial dysfunction in hypertriglyceridemic and diabetic rats http://www.if-pan.krakow.pl/pjp/pdf/2008/1_127.pdf Pharmacological Reports 60 1 127–138 18276994Domagala T. B. Szeffler A. Dobrucki L. W. Dropinski J. Polanski S. Leszczynska-Wiloch M. Kotula-Horowitz K. Wojciechowski J. Wojnowski L. Szczeklik A. Kalinowski L. 2012 Nitric oxide production and endothelium-dependent vasorelaxation ameliorated by N1-methylnicotinamide in human blood vessels Hypertension 59 4 825–832 10.1161/HYPERTENSIONAHA.111.183210 22353616 302943 free anticoagulant,Chlopicki S. Swies J. Mogielnicki A. Buczko W. Bartus M. Lomnicka M. Adamus J. Gebicki J. 2007 1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway British Journal of Pharmacology 152 2 230–239 10.1038/sj.bjp.0707383 1978255 17641676 anti-atherosclerotic, anti-inflammatory,Bryniarski K. Biedron R. Jakubowski A. Chlopicki S. Marcinkiewicz J. 2008 Anti-inflammatory effect of 1-methylnicotinamide in contact hypersensitivity to oxazolone in mice; involvement of prostacyclin https://ruj.uj.edu.pl/xmlui/handle/item/265510 European Journal of Pharmacology 578 2–3 332–338 10.1016/j.ejphar.2007.09.011 17935712 neuroprotective,Fu Lili Liu Caihong Chen Liang Lv Yangge Meng Guoliang Hu Mei Long Yan Hong Hao Tang Susu 2019 Protective Effects of 1-Methylnicotinamide on Aβ1–42-Induced Cognitive Deficits, Neuroinflammation and Apoptosis in Mice http://link.springer.com/10.1007/s11481-018-09830-1 Journal of Neuroimmune Pharmacology en 14 3 401–412 10.1007/s11481-018-09830-1 1557-1890 30635816 subscription and endurance-enhancing effects.Chudzik Michał Burzyńska Monika Kapusta Joanna 2022-07-22 Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients after COVID-19 Nutrients en 14 15 3004 10.3390/nu14153004 2072-6643 9331270 35893858 free Vascular protective effects 1-MNA exerts beneficial effects on blood vessels through its action on the vascular endothelium. It improves the bioavailability of nitric oxide (NO), which is crucial for vasodilation, and regulates the activity of endothelial nitric oxide synthase (eNOS), the enzyme responsible for NO synthesis. These effects have been demonstrated in both in vivo and in vitro studies. Oral administration of 1-MNA has been shown to increase the diameter of the brachial artery (as measured by flow-mediated dilation, FMD) and stimulate NO release from human endothelial cells in both healthy individuals and those with hypercholesterolemia increased. Additionally, in cases of vascular dysfunction (e.g., hypertriglyceridemia or diabetes), 1-MNA restored normal NO-dependent vasodilation. By increasing NO bioavailability, 1-MNA may counteract endothelial dysfunction, support endothelial regeneration, and improve vascular function, particularly in the context of cardiovascular risk. Anticoagulant effects 1-Methylnicotinamide is an endogenous activator of prostacyclin synthesis and can therefore regulate thrombolyticthrombolytic? July 2022 and inflammatory processes in the cardiovascular system. It inhibits platelet-dependent thrombosis through a mechanism involving cyclooxygenase-2 and prostacyclin (PGI2) and increases nitric oxide bioavailability in the endothelium. Endogenous prostacyclin (PGI2) plays a critical role in preventing platelet aggregation and thrombus formation. A deficiency in PGI2 can lead to increased platelet aggregation and arterial thrombi. Anti-atherosclerotic and anti-inflammatory effects 1-MNA exhibits anti-atherosclerotic and anti-inflammatory properties by improving the prostacyclin- and NO-dependent secretory function of the vascular endothelium, inhibiting platelet activation, reducing inflammation within atherosclerotic plaques, and lowering systemic inflammation and TNF-α levels.Mateuszuk L. Jasztal A. Maslak E. Gasior-Glogowska M. Baranska M. Sitek B. Kostogrys R. Zakrzewska A. Kij A. Walczak M. Chlopicki S. 2016-01-22 Antiatherosclerotic Effects of 1-Methylnicotinamide in Apolipoprotein E/Low-Density Lipoprotein Receptor-Deficient Mice: A Comparison with Nicotinic Acid Journal of Pharmacology and Experimental Therapeutics en 356 2 514–524 10.1124/jpet.115.228643 1521-0103 6047228 26631491 The anti-inflammatory effects of 1-MNA are linked to its ability to stimulate endogenous PGI2 secretion and reduce IL-4 and TNF-α levels.Jakubowski Andrzej Sternak Magdalena Jablonski Konrad Ciszek-Lenda Marta Marcinkiewicz Janusz Chlopicki Stefan 2016 1-Methylnicotinamide protects against liver injury induced by concanavalin A via a prostacyclin-dependent mechanism: A possible involvement of IL-4 and TNF-α https://linkinghub.elsevier.com/retrieve/pii/S1567576915302009 International Immunopharmacology en 31 98–104 10.1016/j.intimp.2015.11.032 26709075 subscription These effects are mediated by endothelial mechanisms rather than a direct impact on immune cell function, ensuring that the body's immune response is not weakened.Biedron Rafal Ciszek Marta Tokarczyk Marianna Bobek Malgorzata Kurnyta Maria Slominska Ewa M. Smolenski Ryszard T. Marcinkiewicz Janusz 2008 1-Methylnicotinamide and nicotinamide: two related anti-inflammatory agents that differentially affect the functions of activated macrophages Archivum Immunologiae et Therapiae Experimentalis en 56 2 127–134 10.1007/s00005-008-0009-2 0004-069X 2766500 18373238 NAD+ pptimization 1-MNA is an inhibitor of nicotinamide N-methyltransferase (NNMT). By inhibiting NNMT activity, it regulates NAD+ biosynthesis via the nicotinamide salvage pathway, the primary route for NAD+ synthesis in mammals. By participating in this pathway, 1-MNA optimizes NAD+ levels. Impact on SIRT1 Research published in Nature Medicine indicates that 1-MNA enhances SIRT1 expression and stability.Hong Shangyu Moreno-Navarrete Jose M Wei Xiaojing Kikukawa Yusuke Tzameli Iphigenia Prasad Deepthi Lee Yoonjin Asara John M Fernandez-Real Jose Manuel Maratos-Flier Eleftheria Pissios Pavlos 2015 Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization Nature Medicine en 21 8 887–894 10.1038/nm.3882 1078-8956 4529375 26168293 SIRT1 is an enzyme associated with longevity. Studies using the nematode Caenorhabditis elegans indicate that 1-MNA supplementation may extend lifespan. These studies also link 1-MNA to SIRT1.Schmeisser K. Mansfeld J. Kuhlow D. Weimer S. Priebe S. Heiland I. Birringer M. Groth M. Segref A. Kanfi Y. Price N. L. Schmeisser S. Schuster S. Pfeiffer A. F. Guthke R. 4 2013 Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide Nature Chemical Biology 9 11 693–700 10.1038/nchembio.1352 4076143 24077178 Platzer M. Hoppe T. Cohen H. Y. Zarse K. Sinclair D. A. Ristow M. Neuroprotective effects Animal experiments with diabetic rats have shown that 1-methylnicotinamide positively effects degenerative changes in the brain, allowing cognitive performance to be maintained longer.Kuchmerovska T. Shymanskyy I. Chlopicki S. Klimenko A. 2010 1-Methylnicotinamide (MNA) in prevention of diabetes-associated brain disorders Neurochemistry International 56 2 221–228 10.1016/j.neuint.2009.10.004 19837120 21785102 It also prevents depressive behavior with efficacy comparable to the common antidepressant fluoxetine. This effect is attributed to the reduction of neuroinflammation, pro-inflammatory cytokines (IL-6, TNF-α), and increased expression of BDNF (brain-derived neurotrophic factor), a protein supporting neuron survival and growth.Zhao Jie Zhang Yin Liu Yue Tang Wen-Qian Ji Chun-Hui Gu Jiang-Hong Jiang Bo 2021 Antidepressant-like effects of 1-methylnicotinamide in a chronic unpredictable mild stress model of depression https://linkinghub.elsevier.com/retrieve/pii/S0304394020308053 Neuroscience Letters en 742 135535 10.1016/j.neulet.2020.135535 33248165 subscription The neuroprotective effects of 1-MNA involve shielding against neurotoxins, amyloid-beta plaques in the brain, neuroinflammatory responses, and neuronal apoptosis. It has been shown to improve memory deficits and cognitive functions, suggesting potential for treating neurodegenerative disorders.Milani Zeinab H. Ramsden David B. Parsons Richard B. 2013 Neuroprotective Effects of Nicotinamide N -Methyltransferase and its Metabolite 1-Methylnicotinamide Journal of Biochemical and Molecular Toxicology en 27 9 451–456 10.1002/jbt.21508 free 1095-6670 23868305 Enhancement of physical performance 1-MNA acts as a myokine, supporting the utilization of amino acids for gluconeogenesis in the liver and stimulating lipolysis in adipose tissue, thereby providing energy for muscles.Nejabati Hamid Reza Ghaffari-Novin Mahsa Fathi-Maroufi Nazila Faridvand Yousef Holmberg Hans-Christer Hansson Ola Nikanfar Saba Nouri Mohammad 2022 N1-Methylnicotinamide: Is it Time to Consider it as a Dietary Supplement for Athletes? https://www.eurekaselect.com/201072/article Current Pharmaceutical Design en 28 10 800–805 10.2174/1381612828666220211151204 2078.1/295117 35152860 subscription Studies indicate that 1-MNA supplementation improves exercise tolerance and reduces fatigue. After one month of supplementation with 58 mg of 1-MNA, post-COVID-19 patients reported improved distances in a 6-minute walk test (6MWT), with 92% of participants experiencing better outcomes compared to controls. Additional studies highlight 1-MNA's ability to enhance physical performance by stimulating PGI2 release, protecting microcirculation, and ensuring adequate blood flow to muscle tissues. This mechanism may reduce cardiovascular risks associated with physical exertion, particularly in individuals with impaired endothelial response.Przyborowski Kamil Wojewoda Marta Sitek Barbara Zakrzewska Agnieszka Kij Agnieszka Wandzel Krystyna Zoladz Jerzy Andrzej Chlopicki Stefan 2015 Menezes Gustavo Batista Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice PLOS ONE en 10 6 e0130908 2015PLoSO..1030908P 10.1371/journal.pone.0130908 1932-6203 4482656 26115505 free Commercialization 1-MNA has been approved for use in food products in the form of 1-MNA chloride. The approval process in the European Union was successfully completed by PHARMENA SA. In 2017, the European Food Safety Authority (EFSA) confirmed the safety of 1-MNA chloride in food supplements, leading to its authorization in 2018 under EU Regulation 2018/1123.Implementing regulation - 2018/1123 - EN - EUR-Lex https://eur-lex.europa.eu/eli/reg_impl/2018/1123/oj 2024-12-09 eur-lex.europa.eu en 1-MNA chloride is currently used in dietary supplements.Endotelio – Molekuła przyszłości https://endotelio.eu/en/ 2024-12-09 Endotelio en-GB Other chemical forms of 1-MNA are not currently allowed on the market as food. Safety The safety of 1-MNA chloride has been thoroughly evaluated by EFSA, confirming its safe use. It must meet quality parameters defined in EU Regulation 2018/1123.EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Turck Dominique Bresson Jean-Louis Burlingame Barbara Dean Tara Fairweather-Tait Susan Heinonen Marina Hirsch-Ernst Karen Ildico Mangelsdorf Inge McArdle Harry J Naska Androniki Neuhäuser-Berthold Monika Nowicka Grażyna Pentieva Kristina Sanz Yolanda 2017 Safety of 1-methylnicotinamide chloride (1-MNA) as a novel food pursuant to Regulation (EC) No 258/97 EFSA Journal 15 10 e05001 10.2903/j.efsa.2017.5001 free 7010160 32625296 References Category:Drugs acting on the genito-urinary system Category:Cations Category:Nicotinamides Category:Pyridinium compounds