Levomefolic acid

Source: Wikipedia, the free encyclopedia.

Levomefolic acid
Names
IUPAC name
(2S)-2-[ [4-[(2-Amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl) methylamino]benzoyl]amino]pentanedioic acid
Other names
(L-5-Me-THFA, L-5-Me-H4FA),
anion: L-5-methyltetrahydrofolate (L-5-Me-THF, L-5-Me-H4F), L-methylfolate
Metafolin
Identifiers
3D model (
JSmol
)
ChEBI
ChemSpider
KEGG
MeSH 5-methyltetrahydrofolate
UNII
  • InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12-,13-/m0/s1
    Key: ZNOVTXRBGFNYRX-STQMWFEESA-N
  • InChI=1/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12-,13-/m0/s1
    Key: ZNOVTXRBGFNYRX-STQMWFEEBP
  • CN1c2c([nH]c(nc2=O)N)NC[C@@H]1CNc3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
Properties
C20H25N7O6
Molar mass 459.463 g·mol−1
Pharmacology
B03BB51 (WHO)
oral, transdermal, subcutaneous
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Levomefolic acid (

DHFR) to become biologically active.[1]

It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary

tetrahydrofolate
.

Levomefolic acid is generated by

5,10-methylenetetrahydrofolate (MTHF) and used to recycle homocysteine back to methionine by methionine synthase (MS).[2]

L-Methylfolate is water-soluble and primarily excreted via the kidneys. In a study of 21 subjects with coronary artery disease, peak plasma levels were reached in one to three hours following

ng/ml vs. 14.1 ng/ml).[3]

Metabolism

THF
: tetrahydrofolate.

Medical uses

Major depressive disorder

Research suggests that levomefolic acid (L-methylfolate) taken with a

adjunctive antidepressant effect for individuals who do not respond or have only a partial therapeutic response to SSRI or SNRI medication,[5][6] and might be a more cost-effective adjunctive agent than second-generation antipsychotics.[7]

Cardiovascular disease and cancer

Levomefolic acid (and folic acid in turn) has been proposed for treatment of cardiovascular disease

FdUMP, a metabolite of the drug fluorouracil
.

Patent issues

In March 2012,

Merck & Cie of Switzerland, Pamlab LLC (maker of Metanx and Cerefolin, Neevo DHA, and Deplin), and South Alabama Medical Science Foundation (SAMSF) (the plaintiffs) filed a complaint in the United States District Court for the Eastern District of Texas against four defendants: Macoven Pharmaceuticals (owned by Pernix Therapeutics), Gnosis SpA of Italy, Gnosis U.S.A and Gnosis Bioresearch Switzerland. The plaintiffs alleged that the defendants infringed on several of the plaintiffs' patents.[11] The Macoven products named in the suit are: "Vitaciric-B", "ALZ-NAC", "PNV DHA", and l-methylfolate calcium (levomefolate calcium).[12]

In September 2012, the same three plaintiffs filed a complaint requesting that the International Trade Commission begin a 19 U.S.C. § 1337 investigation of the same four defendants. The complaint states that Gnosis' "Extrafolic-S" and products which are made from it, infringe upon three of their patents: US 5997915 , US 6673381 , and US 7172778 .[13]

Formulations

Levomefolate calcium, a calcium salt of levomefolic acid is sold under the brand name Metafolin[14] and incorporated in Deplin.[15] Levomefolate magnesium is a magnesium salt of levomefolic acid, manufactured as DeltaFolate, a primary ingredient in EnLyte.[16]

See also

References

  1. S2CID 12876272
    .
  2. ^ "5-methyltetrahydrofolate – Compound Summary", PubChem, NCBI, retrieved 25 September 2012
  3. ^ "CerefolinNAC Caplets Package Insert" (PDF).
  4. ^ Sussman, Norman (1 March 2009). "Selecting a First-line Antidepressant: New Analysis". Primary Psychiatry. 16: 19–22.
  5. PMID 34794190
    .
  6. S2CID 245436052
    .
  7. PMID 24372461
    .
  8. PMID 14769778
    .
  9. PMID 11815318.[dead link
    ]
  10. PMID 15870856
    .
  11. ^ The six patents named were US 5997915 , US 6011040 , US 6254904 , US 6673381 , US 7674490  and US 7172778 .
  12. ^ "Pernix Therapeutics' Subsidiary Macoven Pharmaceuticals, LLC Named in Suit by Merck, Pamlab, L.L.C. and Others for Alleged". Bloomberg. 6 March 2012. Retrieved 1 October 2012.
  13. ^ Schweibenz EW (10 September 2012). "SAMSF, Merck, and Pamlab File New 337 Complaint Regarding Certain Reduced Folate Nutraceutical Products and L-methylfolate Raw Ingredients Used Therein". Oblon, Spivak, McClelland, Maier & Neustadt, L.L.P. Archived from the original on 1 October 2012.
  14. ^ "Metafolin". MilliporeSigma. Retrieved 28 November 2022. Metafolin® is our manufactured calcium salt of L-5-methyltetrahydrofolic or L-methylfolate. ... The life science business of Merck KGaA, Darmstadt, Germany operates as MilliporeSigma in the US and Canada.
  15. ^ "DEPLIN®". For Healthcare Professionals. Retrieved 28 November 2022.
  16. ^ "EnLyte with DeltaFolate". dailymed.nlm.nih.gov. Retrieved 28 November 2022.

External links

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