Sadek Bassem, Saad Ali, Sadeq Adel, Jalal Fakhreya, Stark Holger
Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates.
Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates.
Behav Brain Res. 2016 Oct 1;312:415-30. doi: 10.1016/j.bbr.2016.06.051. Epub 2016 Jun 27.
The potential contributions of the brain histaminergic system in neurodegenerative diseases, and the possiblity of histamine-targeting treatments is attracting considerable interests. The histamine H3 receptor (H3R) is expressed mainly in the central nervous system, and is, consequently, an attractive pharmacological target. Although recently described clinical trials have been disappointing in attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCH), numerous H3R antagonists, including pitolisant, demonstrate potential in the treatment of narcolepsy, excessive daytime sleepiness associated with cognitive impairment, epilepsy, and Alzheimer's disease (AD). This review focuses on the recent preclinical as well as clinical results that support the relevance of H3R antagonists for the treatment of cognitive symptoms in neuropsychiatric diseases, namely AD, epilepsy and SCH. The review summarizes the role of histaminergic neurotransmission with focus on these brain disorders, as well as the effects of numerous H3R antagonists on animal models and humans.
脑组胺能系统在神经退行性疾病中的潜在作用以及靶向组胺治疗的可能性正引起广泛关注。组胺H3受体（H3R）主要在中枢神经系统中表达，因此是一个有吸引力的药理学靶点。尽管最近报道的针对注意力缺陷多动障碍（ADHD）和精神分裂症（SCH）的临床试验结果令人失望，但包括匹莫林在内的众多H3R拮抗剂在治疗发作性睡病、与认知障碍相关的日间过度嗜睡、癫痫和阿尔茨海默病（AD）方面显示出潜力。本综述重点关注近期支持H3R拮抗剂治疗神经精神疾病（即AD、癫痫和SCH）认知症状相关性的临床前和临床研究结果。综述总结了组胺能神经传递在这些脑部疾病中的作用，以及众多H3R拮抗剂对动物模型和人类的影响。
