Motawaj Mouhammad, Burban Aude, Davenas Elisabeth, Gbahou Florence, Faucard Raphaël, Morisset Séverine, Arrang Jean-Michel
Laboratoire de Neurobiologie et Pharmacologie Moléculaire, Inserm U894, Centre de Psychiatrie et Neurosciences, Paris, France.
Therapie. 2010 Sep-Oct;65(5):415-22. doi: 10.2515/therapie/2010058. Epub 2010 Dec 13.
The central effects of histamine are mediated by H(1), H(2) and H(3) receptors. The H(3) receptor inhibits histamine release in brain. Therefore, H(3) receptor inverse agonists, by suppressing this brake, enhance histamine neuron activity. The histaminergic system plays a major role in cognition and H(3) receptor inverse agonists are expected to be a potential therapeutics for cognitive deficits of Alzheimer's disease (AD). They are eagerly awaited inasmuch as other treatments of the disease, such as tacrine or memantine, also enhance, through different mechanisms, histaminergic neurotransmission. An important loss of histaminergic neurons has been observed in AD. In contrast, levels of the histamine metabolite in the CSF of AD patients show that their global activity is decreased by only 25%. This indicates that activating histamine neurons in AD can be envisaged.
组胺的中枢效应由H(1)、H(2)和H(3)受体介导。H(3)受体抑制脑内组胺释放。因此，H(3)受体反向激动剂通过抑制这种制动作用来增强组胺能神经元的活性。组胺能系统在认知中起主要作用，H(3)受体反向激动剂有望成为治疗阿尔茨海默病（AD）认知缺陷的潜在药物。鉴于该疾病的其他治疗方法，如他克林或美金刚，也通过不同机制增强组胺能神经传递，人们对H(3)受体反向激动剂翘首以盼。在AD中已观察到组胺能神经元的大量丧失。相比之下，AD患者脑脊液中组胺代谢产物的水平表明，其整体活性仅降低了25%。这表明可以设想激活AD患者的组胺能神经元。
