Anti-cholinergics mecamylamine and scopolamine alleviate motion sickness-induced gastrointestinal symptoms through both peripheral and central actions
Anti-cholinergics mecamylamine and scopolamine alleviate motion sickness-induced gastrointestinal symptoms through both peripheral and central actions
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抗胆碱药美加明和东莨菪碱通过外周和中枢作用减轻晕动病引起的胃肠道症状
DOI：
10.1016/j.neuropharm.2018.12.006
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发表时间：
2019-03
影响因子：
4.7
通讯作者：
Cai Yiling
中科院分区：
文献类型：
--
作者：
Qi Ruirui;Su Yang;Pan Leilei;Mao Yuqi;Liang Lu;Dai Zhiqiang;Wang Junqin;Cai Yiling
增强的胆碱能活性有助于产生复杂的自主表现的运动病（MS）。然而，抗胆碱能药物是否通过中枢或外周作用发挥其抗MS作用仍不清楚。在本研究中，我们研究了美加明（MEC）和东莨菪碱（SCOP）对旋转诱导的大鼠胃肠道症状（条件性张口和排便），运动障碍（活动减少和平衡能力受损），体温降低以及前庭自主神经区Fos表达的影响。观察了六烃季铵（HEX）和甲基东莨菪碱（MSCP）对MS行为反应的影响。还检查了所有这些药物对猫旋转诱导的呕吐和其他MS症状的疗效。我们发现，MEC和SCOP灌胃抑制大鼠旋转诱导的张口和排便，但只有MEC表现出剂量依赖性的方式。MEC加重了旋转引起的平衡障碍，但不能像SCOP那样减轻旋转引起的体温降低。MEC对前庭尾侧核和孤束核Fos表达的抑制作用强于SCOP。腹腔注射HEX和MSCP也能明显减轻旋转诱导的胃肠道症状，并有利于大鼠的平衡能力。在猫中，MEC、SCOP和HEX对旋转诱导的呕吐和流涎有预防作用，并减少非干呕/呕吐症状，但MSCP仅减轻呕吐。提示MEC和SCOP可能通过抑制外周自主神经系统和中枢前庭自主神经通路而减轻MS的胃肠道症状。MEC等烟碱型乙酰胆碱受体抑制剂有望成为治疗MS或其他前庭疾病引起的胃肠道症状的新药物。
Enhanced cholinergic activity contributes to the production of complex autonomic manifestations of motion sickness (MS). However, whether anti-cholinergics exert their anti-MS effects through central or peripheral actions remained unclarified. In the present study, we investigated the effects of mecamylamine (MEC) and scopolamine (SCOP) on rotation-induced gastrointestinal symptoms (conditioned gaping and defecation), locomotion disturbances (hypoactivity and impaired balance performance), hypothermia as well as Fos expression in vestibulo-autonomic regions in rats. We also observed the effects of hexamethonium (HEX) and methyl scopolamine (MSCP) on those MS behavioral responses. The efficacy of all these drugs on rotation-induced emesis and other MS symptoms in cats was also examined. We found that intragastric administration of MEC and SCOP inhibited rotation-induced gaping and defecation in rats, but only MEC showed a dose-dependent manner. MEC aggravated rotation-induced balance disorder and failed to attenuate rotation-induced hypothermia as the SCOP did. MEC was more effective for inhibiting Fos expression in the caudal vestibular nucleus and nucleus of solitary tract than SCOP. Intraperitoneal injection of HEX and MSCP also significantly alleviated rotation-induced gastrointestinal symptoms, and showed benefit to balance performance in rats. In cats, MEC, SCOP and HEX had prophylactic effects against rotation-induced emesis and salivation, and deceased non-retching/vomiting symptoms, but MSCP only attenuated emesis. It suggested that MEC and SCOP might alleviate gastrointestinal symptoms of MS via inhibiting peripheral autonomic nervous system and central vestibulo-autonomic pathways. The nicotinic acetylcholine receptor inhibitors like MEC might be new candidates against gastrointestinal symptoms induced by MS or other vestibular disorders.
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影响因子：
2.9
作者：
Tu, Longlong;Poppi, Lauren;Nalivaiko, Eugene
通讯作者：
Nalivaiko, Eugene
影响因子：
7.4
作者：
S. VanPatten;Y. Al-Abed
通讯作者：
S. VanPatten;Y. Al-Abed
影响因子：
3.7
作者：
Stoffregen TA;Chen FC;Varlet M;Alcantara C;Bardy BG
通讯作者：
Bardy BG
影响因子：
--
作者：
MAKALE, MT;KING, GL
通讯作者：
KING, GL
DOI：
--
发表时间：
1999-12
期刊：
Aviation, space, and environmental medicine
影响因子：
--
作者：
Jokerst;M. Gatto;R. Fazio;R. Stern;K. Koch
通讯作者：
Jokerst;M. Gatto;R. Fazio;R. Stern;K. Koch