Nicotinamide

Nicotinamide
IUPAC name pyridine-3-carboxamide
Other names 3-pyridinecarboxamide niacinamide nicotinamide nicotinic acid amide Vitamin PP
Identifiers
CAS number	98-92-0 Y
PubChem	936
ChemSpider	911 Y
UNII	25X51I8RD4 Y
EC number	202-713-4
DrugBank	DB02701
KEGG	D00036 Y
ChEBI	CHEBI:17154 N
ChEMBL	CHEMBL1140 Y
Jmol-3D images	Image 1
SMILES c1cc(cnc1)C(=O)N
InChI InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9) Y Key: DFPAKSUCGFBDDF-UHFFFAOYSA-N Y InChI=1/C6H6N2O/c7-6(9)5-2-1-3-8- 4-5/h1-4H,(H2,7,9)/f/h7H2 InChI=1/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9) Key: DFPAKSUCGFBDDF-UHFFFAOYAZ
Properties
Molecular formula	C6H6N2O
Molar mass	122.12 g mol−1
Melting point	128-131 °C
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Nicotinamide, also known as niacinamide and nicotinic acid amide, is the amide of nicotinic acid (vitamin B₃ / niacin). Nicotinamide is a water-soluble vitamin and is part of the vitamin B group. Nicotinic acid, also known as niacin, is converted to nicotinamide in vivo, and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacologic and toxic effects of niacin, which occur incidental to niacin's conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,^[1] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.^[2] In cells, niacin is incorporated into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), although the pathways for nicotinamide and nicotinic acid are very similar. NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions.^[3]

Use in medicine

Nicotinamide has demonstrated anti-inflammatory actions that may be of benefit to patients with inflammatory skin conditions.^[4] These conditions include acne vulgaris, and the compound can suppress antigen-induced, lymphocytic transformation and inhibit 3'-5' cyclic AMP phosphodiesterase. Nicotinamide has demonstrated the ability to block the inflammatory actions of iodides known to precipitate or exacerbate inflammatory acne.

Nicomide is the name of an acne medication and, in its vitamin supplement form, the most predominant ingredient is 750 mg of nicotinamide, based on this area of research. Also, it is used topically as a 4% or 5% gel or cream - as effective as topical 1% clindamycin (8-week double-blind trial) performed at the New York University College of Medicine.^[5] Nicotinamide acne treatment is also available as Nicotinamide pads and cream.

Animal studies show that nicotinamide has anti-anxiety (anxiolytic) properties. It may work in a way similar to benzodiazepines.^[6]

Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipidemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are administered orally. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 gm/day and unsupervised use should be discouraged.^[2] In overall, it rarely causes side effects, and is considered generally safe as a food additive, and as a component in cosmetics and medication.^[7]

Nicotinamide is produced by the aqueous aminolysis of 3-cyanopyridine (nicotinonitrile) and subsequent crystallization.

Nicotinamide is an activator of sirtuins (but inhibits at higher doses) and has been reported to restore cognition in Alzheimer's disease transgenic mice.^[8] A safety study of niacinamide for the treatment of Alzheimer's disease is currently underway at the University of California, Irvine.^[9]

Nicotinamide has been reported to increase the endurance of mice.^[10]

Nicotinamide prevents immunosuppression caused by UVA and UVB radiation, and could be added to sunscreen.^[11]

Nicotinamide has been reported to be an effective skin whitener in topical application.^{[12] [13]}

Niacinamide acts as a chemo- and radio-sensitizing agent by enhancing tumor blood flow, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.^[14] PARP-1 appears to be an important target for triple negative breast cancers because the cells are sensitive to inhibition of PARP-1.^[15] Niacinamide is also used by some patients in combination with intravenous vitamin C therapy for cancer.^[16]

Compendial status

• British Pharmacopoeia ^[17]
• Japanese Pharmacopoeia ^[18]

See also

• Nicotinamide adenine dinucleotide
• Isonicotinamide

Notes & references

1. ^ Jacenollo, P. (1992). Niacin versus niacinamide
2. ^ ^{a b} Knip M, Douek IF, Moore WP et al. (2000). "Safety of high-dose nicotinamide: a review". Diabetologia 43 (11): 1337–45. doi:10.1007/s001250051536. PMID 11126400. 
3. ^ Belenky P; Bogan KL, Brenner C (2007). "NAD+ metabolism in health and disease". Trends Biochem. Sci. 32 (1): 12–9. doi:10.1016/j.tibs.2006.11.006. PMID 17161604. http://www.dartmouth.edu/~brenner/belenky07a.pdf. Retrieved 2007-12-23. 
4. ^ Niren NM (2006). "Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review". Cutis 77 (1 Suppl): 11–6. PMID 16871774. 
5. ^ Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK (June 1995). "Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris". International Journal of Dermatology 34 (6): 434–7. doi:10.1111/j.1365-4362.1995.tb04449.x. PMID 7657446. 
6. ^ Tallman JF, Paul SM, Skolnick P, Gallager DW (1980). "Receptors for the age of anxiety: pharmacology of the benzodiazepines". Science 207 (4428): 274–81. doi:10.1126/science.6101294. PMID 6101294. 
7. ^ Cosmetic Ingredient Review Expert Panel (2005). "Final report of the safety assessment of niacinamide and niacin". Int. J. Toxicol. 24 Suppl 5: 1–31. PMID 16596767. 
8. ^ Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM (2008-11-05). "Journal of Neuroscience - Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau". http://www.jneurosci.org/cgi/content/abstract/28/45/11500. Retrieved 2008-11-05. .
9. ^ Safety Study of Nicotinamide to Treat Alzheimer's Disease, clinicaltrials.gov
10. ^ Fukuwatari T, Shibata K, Ishihara K, Fushiki T, Sugimoto E (April 2001). "Elevation of blood NAD level after moderate exercise in young women and mice". J. Nutr. Sci. Vitaminol. 47 (2): 177–9. doi:10.3177/jnsv.47.177. PMID 11508711. 
11. ^ Damian DL, Patterson CR, Stapelberg M, Park J, Barnetson RS, Halliday GM (February 2008). "UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide". J. Invest. Dermatol. 128 (2): 447–54. doi:10.1038/sj.jid.5701058. PMID 17882270. 
12. ^ Hakozaki T, Minwalla L, Zhuang J et al. (July 2002). "The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer". Br. J. Dermatol. 147 (1): 20–31. doi:10.1046/j.1365-2133.2002.04834.x. PMID 12100180. 
13. ^ Navarrete-Solís J, Castanedo-Cázares JP, Torres-Álvarez B et al. (July 2011). "A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma.". Dermatol Res Pract. 2011 (379173). doi:10.1155/2011/379173. PMID 21822427. 
14. ^ Definition of niacinamide, National Cancer Institute
15. ^ Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial.
16. ^ Intravenously administered vitamin C as cancer therapy: three cases
17. ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009". http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf. Retrieved 4 February 2010. 
18. ^ "Japanese Pharmacopoeia, Fifteenth Edition". 2006. http://jpdb.nihs.go.jp/jp15e/JP15.pdf. Retrieved 4 Februally 2010. 

External links

• A11HA01
• DrugBank.ca Drug Card for Nicotinamide