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Histamine N-Methyltransferase in the Brain

1
Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
2
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1, Fukumuro, Miyagino-ku, Sendai 983-8536, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 737; https://doi.org/10.3390/ijms20030737
Received: 24 January 2019 / Revised: 8 February 2019 / Accepted: 8 February 2019 / Published: 10 February 2019
(This article belongs to the Special Issue Histamine-Related Molecules as Therapeutic Targets)
Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood–brain barrier permeability have not been available until now. Recently, we have phenotyped Hnmt-deficient mice to elucidate the importance of HNMT in the central nervous system. Hnmt disruption resulted in a robust increase in brain histamine concentration, demonstrating the essential role of HNMT in the brain histamine system. Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson’s disease and attention deficit hyperactivity disorder. Postmortem studies also have indicated that HNMT expression is altered in human brain diseases. These findings emphasise that an increase in brain histamine levels by novel HNMT inhibitors could contribute to the improvement of brain disorders. View Full-Text
Keywords: diamine oxidase; histamine; histamine H3 receptor; histamine N-methyltransferase diamine oxidase; histamine; histamine H3 receptor; histamine N-methyltransferase
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Yoshikawa, T.; Nakamura, T.; Yanai, K. Histamine N-Methyltransferase in the Brain. Int. J. Mol. Sci. 2019, 20, 737.

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