Α-Fluoromethylhistidine Explained

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

Notes and References

  1. August TF, Musson DG, Hwang SS, Duggan DE, Hooke KF, Roman IJ, Ferguson RJ, Bayne WF . 6 . Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor . Journal of Pharmaceutical Sciences . 74 . 8 . 871–5 . August 1985 . 4032273 . 10.1002/jps.2600740814 .
  2. Watanabe T, Yamatodani A, Maeyama K, Wada H . Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase . Trends in Pharmacological Sciences . 11 . 9 . 363–7 . September 1990 . 2238092 . 10.1016/0165-6147(90)90181-7 .
  3. Thakkar MM . Histamine in the regulation of wakefulness . Sleep Medicine Reviews . 15 . 1 . 65–74 . February 2011 . 20851648 . 3016451 . 10.1016/j.smrv.2010.06.004 .
  4. Monti JM, D'Angelo L, Jantos H, Pazos S . Effects of a-fluoromethylhistidine on sleep and wakefulness in the rat. Short note . Journal of Neural Transmission . 72 . 2 . 141–5 . 1988 . 3385425 . 10.1007/bf01250237 . 20689507 .
  5. Oishi R, Itoh Y, Nishibori M, Saeki K, Ueki S . Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol . Psychopharmacology . 95 . 1 . 77–81 . 1988 . 2838862 . 10.1007/bf00212771 . 43979118 .
  6. Benetti F, Furini CR, de Carvalho Myskiw J, Provensi G, Passani MB, Baldi E, Bucherelli C, Munari L, Izquierdo I, Blandina P . 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 . 25918368 . 4434720 . 10.1073/pnas.1506109112 . 2015PNAS..112E2536B . free .
  7. Ishizuka T, Isono H, Ohtsu H, Yamatodani A . A possible mechanism of alpha-fluoromethylhistidine-induced increase of food intake . Inflammation Research . 53 . S45-6 . March 2004 . Suppl 1 . 15054612 . 10.1007/s00011-003-0321-6 . 6200822 .
  8. Considine KL, Stefanidis L, Grozinger KG, Audie J, Alper BJ . 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 . 28228363 . 10.1016/j.bmcl.2017.02.024 .

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