人组胺H3受体(H3R)最初于1983年在大鼠脑中被描述,并于1999年被克隆。它存在于人脑中,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(自身受体)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、乙酰胆碱和血清素的合成和释放(所有异源受体)。人类组胺 H3 受体有 20 种同工型,其中 8 种是有功能的。H3受体表达于大脑皮层、基底节神经元和海马中,对认知、睡眠和稳态调节过程很重要。此外,组胺 H3R 拮抗剂通过诱导乙酰胆碱的释放来刺激胰岛素释放,并通过引起下丘脑的饱腹感而显着降低肥胖受试者的总体重和甘油三酯。组胺 H3R 拮抗剂降低糖尿病引起的高血糖的能力与二甲双胍相当。因此,有理由声称 H3 受体拮抗剂可能在治疗认知障碍、睡眠能力、氧化应激、炎症和葡萄糖稳态异常方面发挥重要作用。制药公司和大学研究中心正在开发大量的 H3R 拮抗剂。作为这些新药的例子,这篇综述将讨论一些药物,包括第一个产生的组胺 H3R 受体拮抗剂。通过诱导乙酰胆碱的释放,并通过引起下丘脑的饱腹感,显着降低肥胖受试者的总体重和甘油三酯。组胺 H3R 拮抗剂降低糖尿病引起的高血糖的能力与二甲双胍相当。因此,有理由声称 H3 受体拮抗剂可能在治疗认知障碍、睡眠能力、氧化应激、炎症和葡萄糖稳态异常方面发挥重要作用。制药公司和大学研究中心正在开发大量的 H3R 拮抗剂。作为这些新药的例子,这篇综述将讨论一些药物,包括第一个产生的组胺 H3R 受体拮抗剂。通过诱导乙酰胆碱的释放,并通过引起下丘脑的饱腹感,显着降低肥胖受试者的总体重和甘油三酯。组胺 H3R 拮抗剂降低糖尿病引起的高血糖的能力与二甲双胍相当。因此,有理由声称 H3 受体拮抗剂可能在治疗认知障碍、睡眠能力、氧化应激、炎症和葡萄糖稳态异常方面发挥重要作用。制药公司和大学研究中心正在开发大量的 H3R 拮抗剂。作为这些新药的例子,这篇综述将讨论一些药物,包括第一个产生的组胺 H3R 受体拮抗剂。
"点击查看英文标题和摘要"
Histamine H3 receptor antagonists – Roles in neurological and endocrine diseases and diabetes mellitus
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.