nicotinamide

Nicotinamide is the preferred treatment for pellagra, caused by niacin deficiency.

Nicotinamide cream is used as a treatment for acne. It has anti-inflammatory actions, which may benefit people with inflammatory skin conditions.{{cite journal | vauthors = Niren NM | title = Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review | journal = Cutis | volume = 77 | issue = 1 Suppl | pages = 11–6 | date = January 2006 | pmid = 16871774 }}

Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo.{{cite journal | vauthors = Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S | title = Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier | journal = The British Journal of Dermatology | volume = 143 | issue = 3 | pages = 524–31 | date = September 2000 | pmid = 10971324 | doi = 10.1111/j.1365-2133.2000.03705.x | s2cid = 21874670 }} The application of 2% topical nicotinamide for 2 and 4 weeks has been found to be effective in lowering the sebum excretion rate.{{cite journal | vauthors = Draelos ZD, Matsubara A, Smiles K | s2cid = 36713665 | title = The effect of 2% niacinamide on facial sebum production | journal = Journal of Cosmetic and Laser Therapy | volume = 8 | issue = 2 | pages = 96–101 | date = June 2006 | pmid = 16766489 | doi = 10.1080/14764170600717704 }} Nicotinamide has been shown to prevent Cutibacterium acnes-induced activation of toll-like receptor 2, which ultimately results in the down-regulation of pro-inflammatory interleukin-8 production.{{cite journal | vauthors = Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL | title = Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses | journal = Journal of Immunology | volume = 169 | issue = 3 | pages = 1535–41 | date = August 2002 | pmid = 12133981 | pmc = 4636337 | doi = 10.4049/jimmunol.169.3.1535 }}

Nicotinamide at doses of 500 to 1000{{nbsp}}mg a day decreases the risk of skin cancers, other than melanoma, in those at high risk.{{cite journal | vauthors = Snaidr VA, Damian DL, Halliday GM | title = Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety | journal = Experimental Dermatology | volume = 28 | issue = Suppl 1 | pages = 15–22 | date = February 2019 | pmid = 30698874 | doi = 10.1111/exd.13819 | doi-access = free | title-link = doi }}

Nicotinamide has minimal side effects. At very high doses above 3g/ day acute liver toxicity has been documented in at least one case. Normal doses are safe during pregnancy.

The structure of nicotinamide consists of a pyridine ring to which a primary amide group is attached in the meta position. It is an amide of nicotinic acid. As an aromatic compound, it undergoes electrophilic substitution reactions and transformations of its two functional groups. Examples of these reactions reported in Organic Syntheses include the preparation of 2-chloronicotinonitrile by a two-step process via the N-oxide,{{OrgSynth|title = Nicotinamide-1-oxide|year = 1957|volume = 37|pages = 63|doi = 10.15227/orgsyn.037.0063| vauthors = Taylor EC, Crovetti AJ |collvol = 4|collvolpages = 704|prep = CV4P0704}}{{OrgSynth|title = 2-Chloronicitinonitrile|year = 1957|volume = 37|pages = 12|doi = 10.15227/orgsyn.037.0012| vauthors = Taylor EC, Crovetti AJ |collvol = 4|collvolpages = 166|prep = CV4P0166}}

:File:Nicotinamide to 2-chloronicotinonitrile.png

from nicotinonitrile by reaction with phosphorus pentoxide,{{OrgSynth|title = Nicotinonitrile|year = 1953|volume = 33|pages = 52|doi = 10.15227/orgsyn.033.0052| vauthors = Teague PC, Short WA |collvol = 4|collvolpages = 706|prep = CV4P0706}} and from 3-aminopyridine by reaction with a solution of sodium hypobromite, prepared in situ from bromine and sodium hydroxide.{{OrgSynth|title = 3-Aminopyridine|year = 1950|volume = 30|pages = 3|doi = 10.15227/orgsyn.030.0003| vauthors = Allen CF, Wolf CN |collvol = 4|collvolpages = 45|prep = CV4P0045}}

File:Nicotinamide highlighted in NAD+.svg, contains the nicotinamide moiety (highlighted in red)]]

The hydrolysis of nicotinonitrile is catalysed by the enzyme nitrile hydratase from Rhodococcus rhodochrous J1,{{cite journal | vauthors = Nagasawa T, Mathew CD, Mauger J, Yamada H | title = Nitrile Hydratase-Catalyzed Production of Nicotinamide from 3-Cyanopyridine in Rhodococcus rhodochrous J1 | journal = Applied and Environmental Microbiology | volume = 54 | issue = 7 | pages = 1766–1769 | date = July 1988 | pmid = 16347686 | pmc = 202743 | doi = 10.1128/AEM.54.7.1766-1769.1988 | bibcode = 1988ApEnM..54.1766N }}{{cite book|title = White Biotechnology| veditors = Ulber R, Sell D |chapter = Building Blocks|volume = 105|series = Advances in Biochemical Engineering / Biotechnology|isbn = 978-3-540-45695-7|doi = 10.1007/10_033|pmid = 17408083|pages = 133–173|chapter-url = https://books.google.com/books?id=_tXoG93OWHgC&pg=PA141|publisher = Springer Science & Business Media|year = 2007|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=_tXoG93OWHgC&pg=PA141|archive-date = 5 November 2017 | vauthors = Hilterhaus L, Liese A |s2cid = 34552222}}{{cite book|title = Biocatalysis in Organic Synthesis 1|series = Science of Synthesis|publisher = Georg Thieme Verlag|year = 2015|chapter = Enzymatic Synthesis of Amides| vauthors = Schmidberger JW, Hepworth LJ, Green AP, Flitsch SL |pages = 329–372|isbn = 978-3-13-176611-3| veditors = Faber K, Fessner WD, Turner NJ |chapter-url = https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA362|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=8h_wBgAAQBAJ&pg=PA362|archive-date = 5 November 2017}} producing 3500 tons per annum of nicotinamide for use in animal feed.{{cite book|title = Biocatalysis in Organic Synthesis 1|series = Science of Synthesis|publisher = Georg Thieme Verlag|year = 2015|chapter = Hydrolysis of Nitriles to Amides|vauthors = Asano Y |pages = 255–276|isbn = 978-3-13-176611-3| veditors = Faber K, Fessner WD, Turner NJ |chapter-url = https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA256|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=8h_wBgAAQBAJ&pg=PA256|archive-date = 5 November 2017}} The enzyme allows for a more selective synthesis as further hydrolysis of the amide to nicotinic acid is avoided.{{cite journal|title = Biocatalysis| vauthors = Petersen M, Kiener A |doi = 10.1039/A809538H|journal = Green Chem.|year = 1999|volume = 1|issue = 2|pages = 99–106}}{{cite book|title = Biocatalysis in Organic Synthesis 1|series = Science of Synthesis|publisher = Georg Thieme Verlag|year = 2015|chapter = Historical Perspectives: Paving the Way for the Future | vauthors = Servi S, Tessaro D, Hollmann F |pages = 1–39|isbn = 978-3-13-176611-3 | veditors = Faber NJ, Fessner WD, Turner K |chapter-url = https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA7|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=8h_wBgAAQBAJ&pg=PA7|archive-date = 5 November 2017}} Nicotinamide can also be made from nicotinic acid. According to Ullmann's Encyclopedia of Industrial Chemistry, worldwide 31,000 tons of nicotinamide were sold in 2014.

File:NAD+ Oxidation and Reduction.png

Nicotinamide, as a part of the cofactor nicotinamide adenine dinucleotide (NADH / NAD⁺) is crucial to life. In cells, nicotinamide is incorporated into NAD⁺ and nicotinamide adenine dinucleotide phosphate (NADP⁺). NAD⁺ and NADP⁺ are cofactors in a wide variety of enzymatic oxidation-reduction reactions, most notably glycolysis, the citric acid cycle, and the electron transport chain.{{cite journal | vauthors = Belenky P, Bogan KL, Brenner C | title = NAD+ metabolism in health and disease | journal = Trends in Biochemical Sciences | volume = 32 | issue = 1 | pages = 12–9 | date = January 2007 | pmid = 17161604 | doi = 10.1016/j.tibs.2006.11.006 | url = http://www.dartmouth.edu/~brenner/belenky07a.pdf | archive-url = https://web.archive.org/web/20070927170330/http://www.dartmouth.edu/~brenner/belenky07a.pdf | url-status = live | archive-date = 27 September 2007 }} If humans ingest nicotinamide, it will likely undergo a series of reactions that transform it into NAD, which can then undergo a transformation to form NADP⁺. This method of creation of NAD⁺ is called a salvage pathway. However, the human body can produce NAD⁺ from the amino acid tryptophan and niacin without our ingestion of nicotinamide.{{cite journal | vauthors = Williams AC, Cartwright LS, Ramsden DB | title = Parkinson's disease: the first common neurological disease due to auto-intoxication? | journal = QJM | volume = 98 | issue = 3 | pages = 215–26 | date = March 2005 | pmid = 15728403 | doi = 10.1093/qjmed/hci027 | doi-access = free | title-link = doi }}

NAD⁺ acts as an electron carrier that mediates the interconversion of energy between nutrients and the cell's energy currency, adenosine triphosphate (ATP). In oxidation-reduction reactions, the active part of the cofactor is the nicotinamide. In NAD⁺, the nitrogen in the aromatic nicotinamide ring is covalently bonded to adenine dinucleotide. The formal charge on the nitrogen is stabilized by the shared electrons of the other carbon atoms in the aromatic ring. When a hydride atom is added onto NAD⁺ to form NADH, the molecule loses its aromaticity, and therefore a good amount of stability. This higher energy product later releases its energy with the release of a hydride, and in the case of the electron transport chain, it assists in forming adenosine triphosphate.{{cite web|url = http://www.chemistry.wustl.edu/~edudev/LabTutorials/Cytochromes/cytochromes.html|title = Energy for the Body: Oxidative Phosphorylation|website = www.chemistry.wustl.edu|date = 5 September 2008|access-date = 14 March 2017| vauthors = Casiday R, Herman C, Frey R |publisher = Department of Chemistry, Washington University in St. Louis|url-status = live|archive-url = https://web.archive.org/web/20161122122250/http://www.chemistry.wustl.edu/~edudev/LabTutorials/Cytochromes/cytochromes.html|archive-date = 22 November 2016}}

When one mole of NADH is oxidized, 158.2{{nbsp}}kJ of energy will be released.

Nicotinamide occurs as a component of a variety of biological systems, including within the vitamin B family and specifically the vitamin B₃ complex. It is also a critically important part of the structures of NADH and NAD⁺, where the N-substituted aromatic ring in the oxidised NAD⁺ form undergoes reduction with hydride attack to form NADH. The NADPH/NADP⁺ structures have the same ring, and are involved in similar biochemical reactions.

Nicotinamide can be methylated in the liver to biologically active 1-Methylnicotinamide when there are sufficient methyl donors.

Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables.{{cite journal | vauthors = Rolfe HM | s2cid = 28160151 | title = A review of nicotinamide: treatment of skin diseases and potential side effects | journal = Journal of Cosmetic Dermatology | volume = 13 | issue = 4 | pages = 324–8 | date = December 2014 | pmid = 25399625 | doi = 10.1111/jocd.12119 }} It is commonly added to cereals and other foods. Many multivitamins contain 20–30{{nbsp}}mg of vitamin B₃ and it is also available in higher doses.{{cite web|url = http://www.dermnetnz.org/topics/nicotinamide/|title = Nicotinamide|website = DermNet New Zealand (www.dermnetnz.org)|publisher = DermNet New Zealand Trust|access-date = 30 June 2017| vauthors = Ranaweera A |year = 2017|url-status = live|archive-url = https://web.archive.org/web/20170325025401/http://www.dermnetnz.org/topics/nicotinamide/|archive-date = 25 March 2017}}

• British Pharmacopoeia{{cite book|author = British Pharmacopoeia Commission Secretariat|title = Index, BP 2009|year = 2009|url = http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf|access-date = 4 February 2010|url-status = dead|archive-date = 22 July 2011|archive-url = https://web.archive.org/web/20110722134527/http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf}}
• Japanese Pharmacopoeia{{cite book|title = Japanese Pharmacopoeia|edition = 15th|year = 2006|url-status = dead|url = http://jpdb.nihs.go.jp/jp15e/JP15.pdf|access-date = 4 February 2010|archive-date = 22 July 2011|archive-url = https://web.archive.org/web/20110722105441/http://jpdb.nihs.go.jp/jp15e/JP15.pdf}}

A 2015 trial found nicotinamide to reduce the rate of new nonmelanoma skin cancers and actinic keratoses in a group of people at high risk for the conditions.{{cite journal | vauthors = Minocha R, Damian DL, Halliday GM | title = Melanoma and nonmelanoma skin cancer chemoprevention: A{{nbsp}}role for nicotinamide? | journal = Photodermatology, Photoimmunology & Photomedicine | volume = 34 | issue = 1 | pages = 5–12 | date = January 2018 | pmid = 28681504 | doi = 10.1111/phpp.12328 | doi-access = free | title-link = doi }}

Nicotinamide has been investigated for many additional disorders, including treatment of bullous pemphigoid and nonmelanoma skin cancers.{{cite journal | vauthors = Chen AC, Damian DL | title = Nicotinamide and the skin | journal = The Australasian Journal of Dermatology | volume = 55 | issue = 3 | pages = 169–75 | date = August 2014 | pmid = 24635573 | doi = 10.1111/ajd.12163 | s2cid = 45745255 }}

Nicotinamide may be beneficial in treating psoriasis.{{cite journal | vauthors = Namazi MR | title = Nicotinamide: a potential addition to the anti-psoriatic weaponry | journal = FASEB Journal | volume = 17 | issue = 11 | pages = 1377–9 | date = August 2003 | pmid = 12890690 | doi = 10.1096/fj.03-0002hyp | doi-access = free | s2cid = 39752891 }}

There is tentative evidence for a potential role of nicotinamide in treating acne, rosacea, autoimmune blistering disorders, ageing skin, and atopic dermatitis. Nicotinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.{{cite web|url = http://www.cancer.gov/drugdictionary/?CdrID=42044|title = Definition of niacinamide|work = NCI Drug Dictionary|publisher = National Cancer Institute|access-date = 30 June 2017|url-status = live|archive-url = https://web.archive.org/web/20150428051605/http://www.cancer.gov/drugdictionary?cdrid=42044|archive-date = 28 April 2015|date = 2 February 2011}} ARCON (accelerated radiotherapy plus carbogen inhalation and nicotinamide) has been studied in cancer.{{cite journal | vauthors = Kaanders JH, Bussink J, van der Kogel AJ | title = ARCON: a novel biology-based approach in radiotherapy | journal = The Lancet. Oncology | volume = 3 | issue = 12 | pages = 728–37 | date = December 2002 | pmid = 12473514 | doi = 10.1016/s1470-2045(02)00929-4 }}

Research has suggested nicotinamide may play a role in the treatment of HIV.{{cite news | vauthors=Mandavilli A | title=Patient Is Reported Free of H.I.V., but Scientists Urge Caution | website=The New York Times | date=7 July 2020 | url=https://www.nytimes.com/2020/07/07/health/hiv-remission-brazil.html | access-date=22 September 2020 | archive-date=23 September 2020 | archive-url=https://web.archive.org/web/20200923005235/https://www.nytimes.com/2020/07/07/health/hiv-remission-brazil.html | url-status=live }}

Extra-terrestrial nicotinamide has been found in carbonaceous chondrite meteorites.

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