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]
^August TF, Musson DG, Hwang SS, Duggan DE, Hooke KF, Roman IJ, et al. (August 1985). "Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor". Journal of Pharmaceutical Sciences. 74 (8): 871–5.
doi:
10.1002/jps.2600740814.
PMID4032273.
^Watanabe T, Yamatodani A, Maeyama K, Wada H (September 1990). "Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase". Trends in Pharmacological Sciences. 11 (9): 363–7.
doi:
10.1016/0165-6147(90)90181-7.
PMID2238092.
^Monti JM, D'Angelo L, Jantos H, Pazos S (1988). "Effects of a-fluoromethylhistidine on sleep and wakefulness in the rat. Short note". Journal of Neural Transmission. 72 (2): 141–5.
doi:
10.1007/bf01250237.
PMID3385425.
S2CID20689507.
^Oishi R, Itoh Y, Nishibori M, Saeki K, Ueki S (1988). "Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol". Psychopharmacology. 95 (1): 77–81.
doi:
10.1007/bf00212771.
PMID2838862.
S2CID43979118.