Chemistry:α-Fluoromethylhistidine

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α-Fluoromethylhistidine
Alpha-Fluoromethylhistidine.svg
Names
Other names
α-FMH
Identifiers
3D model (JSmol)
ChemSpider
UNII
Properties
C7H10FN3O2
Molar mass 187.174 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

α-Fluoromethylhistidine (α-FMH) is an irreversible specific inhibitor of histidine decarboxylase (HDC).[1] It functions by forming a covalent linkage with a catalytic serine residue on the active site of HDC. Due to its efficacy in reducing histamine levels in tissue mast cells, it has many applications in the study of histaminergic systems.[2]

It has potent sleep-inducing effects in mice.[3][4][5] In the central nervous systems of rats, α-FMH administration has been shown to cause impairments in long-term memory and learning.[6] Additionally, injection of α-FMH has been shown to increase food intake, although the mechanism is believed to distinct from HDC inhibition, indicating that α-FMH may be involved in the regulation of non-histaminergic systems. A proposed mechanism involves the enhanced expression of neuropeptide Y (NPY) rather than HDC inhibition.[7]

α-FMH has also been shown to target isozymes of the glutathione S-transferase (GST) family. Due to the role of GSTs in detoxification, the efficacy of HDC inhibition by α-FMH in humans and its potential for the treatment of pathological conditions is subject to further research.[8]

See also

References

  1. "Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor". Journal of Pharmaceutical Sciences 74 (8): 871–5. August 1985. doi:10.1002/jps.2600740814. PMID 4032273. 
  2. "Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase". Trends in Pharmacological Sciences 11 (9): 363–7. September 1990. doi:10.1016/0165-6147(90)90181-7. PMID 2238092. 
  3. "Histamine in the regulation of wakefulness". Sleep Medicine Reviews 15 (1): 65–74. February 2011. doi:10.1016/j.smrv.2010.06.004. PMID 20851648. 
  4. "Effects of a-fluoromethylhistidine on sleep and wakefulness in the rat. Short note". Journal of Neural Transmission 72 (2): 141–5. 1988. doi:10.1007/bf01250237. PMID 3385425. 
  5. "Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol". Psychopharmacology 95 (1): 77–81. 1988. doi:10.1007/bf00212771. PMID 2838862. 
  6. "Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus". Proceedings of the National Academy of Sciences of the United States of America 112 (19): E2536-42. May 2015. doi:10.1073/pnas.1506109112. PMID 25918368. Bibcode2015PNAS..112E2536B. 
  7. "A possible mechanism of alpha-fluoromethylhistidine-induced increase of food intake". Inflammation Research 53 Suppl 1: S45-6. March 2004. doi:10.1007/s00011-003-0321-6. PMID 15054612. 
  8. "Efficient synthesis of α-fluoromethylhistidine di-hydrochloride and demonstration of its efficacy as a glutathione S-transferase inhibitor". Bioorganic & Medicinal Chemistry Letters 27 (6): 1335–1340. March 2017. doi:10.1016/j.bmcl.2017.02.024. PMID 28228363.