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Histamine N-Methyltransferase in the Brain

Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
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;
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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MDPI and ACS Style

Yoshikawa, T.; Nakamura, T.; Yanai, K. Histamine N-Methyltransferase in the Brain. Int. J. Mol. Sci. 2019, 20, 737.

AMA Style

Yoshikawa T, Nakamura T, Yanai K. Histamine N-Methyltransferase in the Brain. International Journal of Molecular Sciences. 2019; 20(3):737.

Chicago/Turabian Style

Yoshikawa, Takeo, Tadaho Nakamura, and Kazuhiko Yanai. 2019. "Histamine N-Methyltransferase in the Brain" International Journal of Molecular Sciences 20, no. 3: 737.

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