Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain.
Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain.
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DOI：
10.1016/s0024-3205(02)02276-2
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发表时间：
2002-12
期刊：
影响因子：
6.1
通讯作者：
M. Tashiro;H. Mochizuki;Kentaro Iwabuchi;Yumiko Sakurada;M. Itoh;Takehiko Watanabe;K. Yanai
中科院分区：
文献类型：
--
作者：
M. Tashiro;H. Mochizuki;Kentaro Iwabuchi;Yumiko Sakurada;M. Itoh;Takehiko Watanabe;K. Yanai
脑组胺主要通过与组胺H1受体（H1 Rs）的相互作用参与广泛的生理功能，例如调节睡眠-觉醒周期、觉醒、认知和记忆。产生组胺的神经元，即组胺能神经元，专门位于下丘脑后部，并将组胺传递到大脑的几乎所有区域。组胺H1拮抗剂，或抗组胺药，通常用于治疗过敏性疾病，有时会引起嗜睡和认知缺陷。应当理解，这种CNS副作用的机制是抗组胺药阻断脑中的H1 R。本研究的目的是比较不同的抗组胺药的中枢神经系统副作用。使用斯坦福大学嗜睡量表（SSS）测量主观嗜睡，并通过速示器测试系统检查健康年轻日本志愿者（16名男性，20-28岁）的心理表现。在口服抗组胺药如非索非那定（FEX）和西替利嗪（CET）之前和之后。此外，在8名志愿者中，通过PET与11 C-多塞平检查抗组胺药的H1 R占用。SSS和心理测验结果表明，FEX的镇静作用比CET弱，但差异无统计学意义。PET测量显示，大脑皮层中没有H1 Rs被FEX占据，而约30%的H1 Rs被CET占据。总之，已证实组胺和H1 R参与维持人类的觉醒和认知，并且临床症状的严重程度与渗透到大脑中的抗组胺剂的量相关。
Brain histamine is involved in a wide range of physiological functions such as regulation of the sleep-wake cycle, arousal, cognition, and memory mainly through interactions with histamine H1 receptors (H1Rs). Neurons producing histamine, histaminergic neurons, are exclusively located in the posterior hypothalamus and transmit histamine to almost all regions of the brain. Histamine H1 antagonists, or antihistamines, often prescribed for treatment of allergic disorders, sometimes induce sleepiness and cognitive deficits. It is understood that the mechanism of such CNS side effects is that antihistamine blocks H1Rs in the brain. The purpose of the present study was to compare the CNS side effects of different antihistamines. Subjective sleepiness was measured using the Stanford Sleepiness Scale (SSS) and psychomotor performance was examined by a tachistoscope testing system in healthy, young, Japanese volunteers (16 males, 20–28 yrs.) before and after oral administration of antihistamines such as fexofenadine (FEX) and cetirizine (CET). Additionally, H1R occupancy by antihistamines was examined by PET with11C-doxepin in 8 volunteers. The results of SSS and psychomotor tests demonstrated that FEX tended to be less sedative than CET though the difference was not statistically significant. PET measurements revealed that no H1Rs in the cerebral cortex were occupied by FEX while about 30% of H1Rs were occupied by CET. In summary, it was confirmed that histamine and H1Rs are involved in maintaining arousal and cognition in humans, and that the severity of clinical symptoms is correlated to the amount of antihistamine that penetrated into the brain.