This article is missing information about drugbox or more Chembox Pharmacology.(January 2021) |
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Names | |
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Preferred IUPAC name 2-Methylnaphthalene-1,4-dione | |
Other names Menaphthone; Vitamin K3; β-Methyl-1,4-naphthoquinone; 2-Methyl-1,4-naphthodione; 2-Methyl-1,4-naphthoquinone | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChEMBL | |
ChemSpider | |
DrugBank | |
ECHA InfoCard | 100.000.338 |
KEGG | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C11H8O2 | |
Molar mass | 172.183 g·mol−1 |
Appearance | Bright yellow crystals |
Density | 1.225g/cm3 |
Melting point | 105 to 107 °C (221 to 225 °F; 378 to 380 K) |
Insoluble | |
Pharmacology | |
B02BA02 ( WHO ) | |
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Legal status |
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Hazards | |
Flash point | 113.8 °C (236.8 °F; 386.9 K) |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | 0.5 g/kg (oral, mouse) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Menadione is a synthetic [3] [4] organic compound with the formula C6H4(CO)2C2H(CH3). It is an analog of 1,4-naphthoquinone with a methyl group in the 2-position. [5] It is sometimes called vitamin K3. Use is allowed as a nutritional supplement in animal feed because of its vitamin K activity.
Menadione is converted to vitamin K2 (specifically, MK-4) by the prenyltransferase action of vertebrate UBIAD1. [4] This reaction requires the hydroquinone (reduced) form of K3, menadiol, produced by NQO1. [6]
Menadione is also a circulating form of vitamin K, produced in small amounts (1–5%) after intestinal absorption of K1 and K2. This circulation explains the uneven tissue distribution of MK-4, especially since menadione can penetrate the blood–brain barrier. The cleavage enzyme is yet to be identified. As K3 is known to be toxic in large amounts, researchers speculate that the cleavage process is closely regulated. [6]
The compound is variously known as vitamin K3 [7] and provitamin K3. [8] Proponents of the latter name generally argue that the compound is not a real vitamin due to its artificial status (prior to its identification as a circulating intermediate) and its lack of a 3-methyl side chain preventing it from exerting all the functions (specifically, it cannot act as a cofactor for GGCX in vitro) [9] of the K vitamins.
It is an intermediate in the chemical synthesis of vitamin K by first reduction to the diol menadiol, which is susceptible to coupling to the phytol. [10] It is a useful intermediate for organic synthesis in general, as it can be made and modified in a number of ways. [11]
Menadione can be used to generate reactive oxygen species to perform flow cytometry analysis on. It can also be used in microbiological evaluation to, for example, detect fastidious microorganisms. [12]
In the United States, menadione is used in various types of animal feed and is described as having a history of safe use for this purpose, being used in poultry feed prior to 1958. [13]
Low-dose menadione is used as an inexpensive micronutrient for livestock in many countries. Forms of menadione are also included in some pet foods in developed countries as a source of vitamin K. These doses have yielded no reported cases of toxicity from menadione in livestock or pets. Although handling may be hazardous, the European Food Safety Authority found in 2013 that it is an effective source of vitamin K in animal nutrition that does not pose a risk to the environment. [14]
Despite the fact that it can serve as a precursor to various types of vitamin K, menadione is generally not used as a nutritional supplement in economically developed countries. Menadione for human use at pharmaceutical strength is available in some countries with large lower income populations, such as India. [2] The typical daily dose is 10 mg oral or 2 mg parenteral. [15] It is used in the treatment of hypoprothrombinemia outside of the United States. [2]
Menadione is not believed to be carcinogenic. [16] K3 can cause generation of reactive oxygen species (ROS) by redox cycling and arylation of thiols using its reactive 3-position. [6] ROS generation explains various toxic effects of excessive menadione, including DNA damage and cell death, [16] or on a whole-animal level, cardiac and renal toxicity in rats. [17]
Amygdalin is a naturally occurring chemical compound found in many plants, most notably in the seeds of apricots, bitter almonds, apples, peaches, cherries and plums, and in the roots of manioc.
Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation or for controlling binding of calcium in bones and other tissues. The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma-glutamyl carboxylase that uses vitamin K as a cofactor.
Pantothenic acid (vitamin B5) is a B vitamin and an essential nutrient. All animals need pantothenic acid in order to synthesize coenzyme A (CoA), which is essential for cellular energy production and for the synthesis and degradation of proteins, carbohydrates, and fats.
Tocopherols are a class of organic compounds comprising various methylated phenols, many of which have vitamin E activity. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, it was named tocopherol, from Greek τόκοςtókos 'birth' and φέρεινphérein 'to bear or carry', that is 'to carry a pregnancy', with the ending -ol signifying its status as a chemical alcohol.
Vitamin B6 is one of the B vitamins, and is an essential nutrient for humans. The term essential nutrient refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.
Neohesperidin dihydrochalcone, sometimes abbreviated to neohesperidin DC or simply NHDC, is an artificial sweetener derived from citrus.
Phytomenadione, also known as vitamin K1 or phylloquinone, is a vitamin found in food and used as a dietary supplement. It is on the World Health Organization's List of Essential Medicines.
Menatetrenone (INN), also known as menaquinone-4 (MK-4), is one of the nine forms of vitamin K2.
Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin.
In enzymology, a NAD(P)H dehydrogenase (quinone) (EC 1.6.5.2) is an enzyme that catalyzes the chemical reaction
Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.
Vitamin K deficiency results from insufficient dietary vitamin K1 or vitamin K2 or both.
Menadiol is an organic compound with the formula C6H4(COH)2(CH)(CH3). It is formally a derivative of p-hydroquinone. The name vitamin K4 can refer to:
Selenium yeast is a feed additive for livestock, used to increase the selenium content in their fodder. It is a form of selenium currently approved for human consumption in the EU and Britain. Inorganic forms of selenium are used in feeds. Since these products can be patented, producers can demand premium prices. It is produced by fermenting Saccharomyces cerevisiae in a selenium-rich media.
Naphthoquinones constitute a class of organic compounds structurally related to naphthalene. Two isomers are common for the parent naphthoquinones:
Selenium is an essential micronutrient for animals, though it is toxic in large doses. In plants, it sometimes occurs in toxic amounts as forage, e.g. locoweed. Selenium is a component of the amino acids selenocysteine and selenomethionine. In humans, selenium is a trace element nutrient that functions as cofactor for glutathione peroxidases and certain forms of thioredoxin reductase. Selenium-containing proteins are produced from inorganic selenium via the intermediacy of selenophosphate (PSeO33−).
Vitamin K2 or menaquinone (MK) is one of three types of vitamin K, the other two being vitamin K1 (phylloquinone) and K3 (menadione). K2 is both a tissue and bacterial product (derived from vitamin K1 in both cases) and is usually found in animal products or fermented foods.
Intravenous Ascorbic Acid or PAA, pharmacologic ascorbic acid, is a process that delivers soluble ascorbic acid directly into the bloodstream. It is not approved for use to treat any medical condition.
4-Amino-2-methyl-1-naphthol is a menadione analog. Its water-soluble hydrochloride (HCl) salt is often called vitamin K5. The HCl salt has been used as a medicine for vitamin K deficiency under tradenames such as Synkamin, which was sold by Parke-Davis, but has since been discontinued.
Threshold dose is the minimum dose of drug that triggers minimal detectable biological effect in an animal. At extremely low doses, biological responses are absent for some of the drugs. The increase in dose above threshold dose induces an increase in the percentage of biological responses. Several benchmarks have been established to describe the effects of a particular dose of drug in a particular species, such as NOEL(no-observed-effect-level), NOAEL(no-observed-adverse-effect-level) and LOAEL(lowest-observed-adverse-effect-level). They are established by reviewing the available studies and animal studies. The application of threshold dose in risk assessment safeguards the participants in human clinical trials and evaluates the risks of chronic exposure to certain substances. However, the nature of animal studies also limits the applicability of experimental results in the human population and its significance in evaluating potential risk of certain substances. In toxicology, there are some other safety factors including LD50, LC50 and EC50.