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.
Int J Mol Sci. 2019 Feb 10;20(3):737. doi: 10.3390/ijms20030737.
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 -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 -deficient mice to elucidate the importance of HNMT in the central nervous system. 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 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.
脑内组胺是一种神经递质，调节多种生理功能。先前的研究表明，组胺耗竭参与了几种神经疾病，这表明针对脑内组胺系统的药物开发的重要性。组氨酸-甲基转移酶（HNMT）是一种在脑中表达的组胺代谢酶。尽管使用 HNMT 抑制剂进行了药理学研究，以揭示 HNMT 直接参与脑功能，但直到现在还没有具有高特异性和足够血脑屏障通透性的 HNMT 抑制剂。最近，我们对 - 缺陷小鼠进行了表型分析，以阐明 HNMT 在中枢神经系统中的重要性。 缺失导致脑组胺浓度的显著增加，证明了 HNMT 在脑组胺系统中的重要作用。临床研究表明，人类 基因的单核苷酸多态性与几种脑疾病有关，如帕金森病和注意缺陷多动障碍。尸检研究还表明，HNMT 表达在人类脑疾病中发生改变。这些发现强调了新型 HNMT 抑制剂增加脑组胺水平可能有助于改善脑疾病。
