nicotinic acid amide
|AHFS/Drugs.com||Consumer Drug Information|
|by mouth, topical|
|Chemical and physical data|
|Molar mass||122.13 g·mol−1|
|3D model (JSmol)|
|Density||1.40 g/cm3 g/cm3|
|Melting point||129.5 °C (265.1 °F)|
|Boiling point||334 °C (633 °F)|
Nicotinamide (NAM), also known as niacinamide, is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, nicotinamide has the benefit of not causing skin flushing. As a cream, it is used to treat acne.
Side effects are minimal. At high doses liver problems may occur. Normal amounts are safe for use during pregnancy. Nicotinamide is in the vitamin B family of medications, specifically the vitamin B3 complex. It is an amide of nicotinic acid. Foods that contain nicotinamide include yeast, meat, milk, and green vegetables.
Nicotinamide was discovered between 1935 and 1937. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Nicotinamide is available as a generic medication and over the counter. In the United Kingdom a 60 g tube costs the NHS about £7.10. Commercially nicotinamide is made from either nicotinic acid or 3-cyanopyridine. In a number of countries grains have nicotinamide added to them.
Nicotinamide is the preferred treatment for niacin deficiency (pellagra). A patient's diagnosis of pellagra is based on their history, as well as a presence of dermatitis, diarrhea, and dementia. While nicotinic acid (niacin) may be used, nicotinamide has the benefit of not causing skin flushing.
It has anti-inflammatory actions. These may be of benefit to people with inflammatory skin conditions.
Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo. The application of 2% topical nicotinamide for 2 and 4 weeks has been found to be effective in lowering the sebum excretion rate in study participants. Nictotinamide has been shown to prevent Propionibacterium acnes-induced activation of toll-like receptor (TLR)-2, which ultimately results in the down-regulation of pro-inflammatory IL-8 production.
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,
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.
The hydrolysis of 3-cyanopyridine (nicotinonitrile) is catalysed by the enzyme nitrile hydratase from Rhodococcus rhodochrous J1, producing 3500 tons per annum of nicotinamide for use in animal feed. The enzyme allows for a more selective synthesis as further hydrolysis of the amide to nicotinic acid is avoided. Nicotinamide can also be made from nicotinic acid. According to Ullmann's Encyclopedia of Industrial Chemistry, worldwide sales of nicotinamide were 31,000 tons in 2014.
Nicotinamide, as a part of the coenzyme 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 coenzymes in a wide variety of enzymatic oxidation-reduction reactions the most notable being glycolysis, the citric acid cycle, and the electron transport chain. 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.
NAD+ acts as an electron carrier that helps with the interconversion of energy between nutrients and the cell's energy currency, ATP. In oxidation-reduction reactions, the active part of the coenzyme 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.
For every one mole of NADH that is oxidized, 158.2 kJ of energy will be released.
Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables. It is commonly added to cereals and other foods. If one would want to take it orally, it is present in many multivitamins, and there are around 20–30 mg in each. It is also available as a standalone vitamin, in much higher quantities around 500 mg.
It has been investigated for many disorders, including treatment of bullous pemphigoid nonmelanoma skin cancers. There is also tentative evidence for its effective use to treat autoimmune blistering disorders, acne, rosacea, ageing skin and atopic dermatitis. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy. Niacinamide may be beneficial in treating psoriasis.
Nicotinamide can prevent and even reverse the progression of glaucoma in mice and slows, or even stops damage to retinal ganglion cells and their axons in the optic nerve.
A 2015 trial found that for people at high risk, nicotinamide reduces the rate of new nonmelanoma skin cancers and actinic keratoses.
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