Misplaced Pages

Menatetrenone: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively
Page 1
Page 2
← Previous editContent deleted Content addedVisualWikitext
Revision as of 00:20, 19 September 2011 editGreensburger (talk | contribs)Extended confirmed users11,045 editsNo edit summary← Previous edit Latest revision as of 14:42, 25 January 2024 edit undoMaxim Masiutin (talk | contribs)Extended confirmed users, IP block exemptions, Pending changes reviewers31,043 edits Added s2cid. Added the cs1 style template to denote Vancouver ("vanc") citation style, because references contain "vauthors" attribute to specify the list of authors. 
(87 intermediate revisions by 38 users not shown)
Line 1: Line 1:
{{Short description|Form of vitamin K}}
{{Drugbox
{{cs1 config|name-list-style=vanc}}
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed | Watchedfields = changed
| verifiedrevid = 407767225 | verifiedrevid = 451239229
| IUPAC_name = 2-methyl-3-naphthoquinone | IUPAC_name = 2-methyl-3-naphthoquinone
| image = Menatetrenone.PNG | image = Menatetrenone.PNG
| alt = Structural formula of menatetrenone
| width = 240 | width = 260
| image2 = Menatetrenone molecule spacefill.png
| alt2 = Space-filling model of the menatetrenone molecule


<!--Clinical data--> <!--Clinical data-->
Line 11: Line 16:
| Drugs.com = {{drugs.com|international|menatetrenone}} | Drugs.com = {{drugs.com|international|menatetrenone}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = | pregnancy_category =
⚫ | routes_of_administration = ]
⚫ | ATC_prefix = M05
⚫ | ATC_suffix = BX08

| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = | legal_status =
⚫ | routes_of_administration = Oral


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = | bioavailability = Low (oral)<ref name=avail/>
| protein_bound = | protein_bound =
| metabolism = | metabolism =
| elimination_half-life = | elimination_half-life =
| excretion = | excretion =


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 863-61-6 | CAS_number = 863-61-6
⚫ | ATC_prefix = none
⚫ | ATC_suffix =
| PubChem = 5282367 | PubChem = 5282367
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank =
| UNII_Ref = {{fdacite|changed|FDA}} | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 4445530
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 27Y876D139 | UNII = 27Y876D139
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00100 | KEGG = D00100
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 78277


<!--Chemical data--> <!--Chemical data-->
| C=31 | H=40 | O=2 | C=31 | H=40 | O=2
| molecular_weight = 444.648 g/mol
| synonyms = <small>3-methyl-2-naphthalene-1,4-dione</small> | synonyms = <small>3-methyl-2-naphthalene-1,4-dione</small>
| smiles = CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C31H40O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,12,14,16,18-20H,9-11,13,15,17,21H2,1-6H3/b23-14+,24-16+,25-20+
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = DKHGMERMDICWDU-GHDNBGIDSA-N
}} }}


'''Menatetrenone''' (]), also known as MK4, is a ] compound used as a ] agent and as adjunctive therapy for the pain of ]. It is marketed for the latter indication in ] by ], under the trade name '''Glakay'''. '''Menatetrenone''' (]), also known as '''menaquinone-4''' ('''MK-4'''), is one of the nine forms of ].


== Biology ==
Menatetrenone (MK4) is one of the nine forms of ].<ref name="pmid17274493">{{cite journal |author=Iwamoto J, Takeda T, Sato Y |title=Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis |journal=Nutr. Rev. |volume=64 |issue=12 |pages=509–17 |year=2006 |month=December |pmid=17274493 |doi= 10.1111/j.1753-4887.2006.tb00184.x|url=http://openurl.ingenta.com/content/nlm?genre=article&issn=0029-6643&volume=64&issue=12&spage=509&aulast=Iwamoto}}</ref>
MK-4 is the major form of Vitamin K in vertebrate animals, including humans and common forms of meat animals. It is produced via conversion of vitamin K<sub>1</sub> in the body, specifically in the testes, pancreas and arterial walls.<ref>{{cite journal | vauthors = Shearer MJ, Newman P | title = Metabolism and cell biology of vitamin K | journal = Thrombosis and Haemostasis | volume = 100 | issue = 4 | pages = 530–47 | date = October 2008 | pmid = 18841274 | doi = 10.1160/TH08-03-0147 | s2cid = 7743991 }}</ref> The conversion is not dependent on gut bacteria, occurring in germ-free rats<ref name="Davidson">{{cite journal | vauthors = Davidson RT, Foley AL, Engelke JA, Suttie JW | title = Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria | journal = The Journal of Nutrition | volume = 128 | issue = 2 | pages = 220–3 | date = February 1998 | pmid = 9446847 | doi = 10.1093/jn/128.2.220 | doi-access = free }}</ref><ref name="Ronden">{{cite journal | vauthors = Ronden JE, Drittij-Reijnders MJ, Vermeer C, Thijssen HH | title = Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1379 | issue = 1 | pages = 69–75 | date = January 1998 | pmid = 9468334 | doi = 10.1016/S0304-4165(97)00089-5 }}</ref> and in parenterally-administered K<sub>1</sub> in rats.<ref>{{cite journal | vauthors = Thijssen HH, Drittij-Reijnders MJ | title = Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4 | journal = The British Journal of Nutrition | volume = 72 | issue = 3 | pages = 415–25 | date = September 1994 | pmid = 7947656 | doi = 10.1079/BJN19940043 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Will BH, Usui Y, Suttie JW | title = Comparative metabolism and requirement of vitamin K in chicks and rats | journal = The Journal of Nutrition | volume = 122 | issue = 12 | pages = 2354–60 | date = December 1992 | pmid = 1453219 | doi = 10.1093/jn/122.12.2354 | doi-access = free }}</ref> Tissues that accumulate high amounts of MK-4 have a capacity to convert up to 90% of the available K<sub>1</sub> into MK-4.<ref name="Davidson" /><ref name="Ronden" />{{dubious|reason=Shearer reports that the two article show high conversion of menadione but variable conversion of K1|date=July 2023}}


K<sub>1</sub> is converted to MK-4 in three steps:<ref name="Shearer">{{cite journal | vauthors = Shearer MJ, Newman P | title = Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis | journal = Journal of Lipid Research | volume = 55 | issue = 3 | pages = 345–362 | date = March 2014 | pmid = 24489112 | pmc = 3934721 | doi = 10.1194/jlr.R045559 |doi-access=free }}</ref>
==See also==
* Removal of the phytyl tail to form ] (K3; unknown enzyme);
⚫ * ]
* Reduction of ] to ] (likely ]);
* ] (vitamin K<sub>1</sub>)
* Attachment of GGPP tail to form menaquinol-4, the reduced form of MK-4 (])


The second and third steps are known to happen in target tissue. The first step is proposed to happen mainly in the intestines.<ref name="Shearer"/>
⚫ ==References==
⚫ {{reflist}}


==As a medication==
==External links==
Menatetrenone is approved in Japan for second-line treatment of ]. Evidence is restricted to small-scale RCTs; the minimum effective dose (for bone mass parameters) is 45&nbsp;mg, much higher than the ] for vitamin K (80&nbsp;μg).<ref name=Iwamoto>{{cite journal | vauthors = Iwamoto J | title = Vitamin K<sub>2</sub> therapy for postmenopausal osteoporosis | journal = Nutrients | volume = 6 | issue = 5 | pages = 1971–80 | date = May 2014 | pmid = 24841104 | pmc = 4042573 | doi = 10.3390/nu6051971 | doi-access = free |quote=administered daily doses of 15, 45, 90, and 135 mg revealed that 45 mg was the minimum effective dose for improving bone mass parameters evaluated by microdensitometry and/or single photon absorptiometry in postmenopausal women with osteoporosis}}</ref>
*{{en icon}} {{cite web | url = http://www2.eisai.co.jp/di2/EPI/GLA_SC_EPI.pdf | title = Glakay | month = November | year = 2005 | accessdate = 2007-03-06 | format = PDF | publisher = ]}} {{Dead link|date=October 2010|bot=H3llBot}} Product information.


=== Bioavailbility and dose ===
420&nbsp;μg of oral MK-4, in a single-dose or spread out over 7 days, does not cause detectable changes in serum MK-4 level in healthy women, whereas MK-7 produces the expected increases in MK-7 levels.<ref name=avail>{{cite journal | vauthors = Sato T, Schurgers LJ, Uenishi K | title = Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women | journal = Nutrition Journal | volume = 11 | issue = 93 | pages = 93 | date = November 2012 | pmid = 23140417 | pmc = 3502319 | doi = 10.1186/1475-2891-11-93 | doi-access = free }}</ref>


The minimum effective oral dose to change serum ] levels is 1500&nbsp;μg/d, where as oral MK-7 is effective on this parameter at 45&nbsp;μg/d, a level more in line with nutritional intake. In addition, rat studies show that oral MK-7 is better at increasing extrahepatic tissue levels of MK-4 than oral MK-4.<ref name=avail/>
⚫ {{Vitamin}}
⚫ ]
⚫ ]


⚫ == References ==
⚫ {{reflist}}


{{Spoken Misplaced Pages|MenatetrenoneA.ogg|date=2012-09-08}}
{{gastrointestinal-drug-stub}}


{{Drugs for treatment of bone diseases}}
]
⚫ {{Vitamin}}
{{Prostanoidergics}}

⚫ ]
⚫ ]
⚫ ]