Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, United Arab Emirates.
Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, United Arab Emirates.
Biomed Pharmacother. 2022 Jun;150:112947. doi: 10.1016/j.biopha.2022.112947. Epub 2022 Apr 19.
Human histamine H3 receptor (H3R) was initially described in the brain of rat in 1983 and cloned in 1999. It can be found in the human brain and functions as a regulator of histamine synthesis and release. H3 receptors are predominantly resident in the presynaptic region of neurons containing histamine, where they modulate the synthesis and release of histamine (autoreceptor) or other neurotransmitters such as dopamine, norepinephrine, gamma-aminobutyric acid (GABA), glutamate, acetylcholine and serotonin (all heteroreceptors). The human histamine H3 receptor has twenty isoforms of which eight are functional. H3 receptor expression is seen in the cerebral cortex, neurons of the basal ganglia and hippocampus, which are important for process of cognition, sleep and homoeostatic regulation. In addition, histamine H3R antagonists stimulate insulin release, through inducing the release of acetylcholine and cause significant reduction in total body weight and triglycerides in obese subjects by causing a feeling of satiety in the hypothalamus. The ability of histamine H3R antagonist to reduce diabetes-induced hyperglycaemia is comparable to that of metformin. It is reasonable therefore, to claim that H3 receptor antagonists may play an important role in the therapy of disorders of cognition, the ability to sleep, oxidative stress, inflammation and anomaly of glucose homoeostasis. A large number of H3R antagonists are being developed by pharmaceutical companies and university research centres. As examples of these new drugs, this review will discuss a number of drugs, including the first histamine H3R receptor antagonist produced.
人类组胺 H3 受体（H3R）于 1983 年在大鼠脑中首次描述，并于 1999 年克隆。它可以在人脑内发现，作为组胺合成和释放的调节剂。H3 受体主要存在于含有组胺的神经元的突触前区域，在那里它们调节组胺（自受体）或其他神经递质如多巴胺、去甲肾上腺素、γ-氨基丁酸（GABA）、谷氨酸、乙酰胆碱和血清素（所有异受体）的合成和释放。人类组胺 H3 受体有二十种亚型，其中八种是有功能的。H3 受体表达可见于大脑皮层、基底神经节和海马体的神经元，这些对认知、睡眠和体内平衡调节过程很重要。此外，组胺 H3R 拮抗剂通过诱导乙酰胆碱释放刺激胰岛素释放，并通过在下丘脑中引起饱腹感，导致肥胖受试者的体重和甘油三酯显著降低。组胺 H3R 拮抗剂降低糖尿病引起的高血糖的能力可与二甲双胍相媲美。因此，可以合理地声称，H3 受体拮抗剂可能在认知障碍、睡眠能力、氧化应激、炎症和葡萄糖体内平衡异常的治疗中发挥重要作用。许多制药公司和大学研究中心正在开发 H3R 拮抗剂。作为这些新药的例子，本综述将讨论一些药物，包括第一个组胺 H3R 受体拮抗剂。
