Tsujimura Takanori, Sakai Shogo, Suzuki Taku, Ujihara Izumi, Tsuji Kojun, Magara Jin, Canning Brendan J, Inoue Makoto
Division of Dysphagia Rehabilitation, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; and
Division of Dysphagia Rehabilitation, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; and.
Am J Physiol Gastrointest Liver Physiol. 2017 May 1;312(5):G498-G507. doi: 10.1152/ajpgi.00299.2016. Epub 2017 Mar 2.
Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam, and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation. The effects of intraperitoneal or topical administration of each drug on swallowing function were studied. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA receptor antagonist diminished the effects of baclofen. Topically applied diazepam or baclofen had no effect on swallowing. These data indicate that diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA receptor antagonist diminished the effects of baclofen. Topical applied diazepam or baclofen was without effect on swallowing. Diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats.
吞咽困难不仅由神经和/或结构损伤引起，还由药物导致。我们推测美金刚、右美沙芬、地西泮和巴氯芬这些作用于中枢的常用药物可能会调节吞咽功能。在麻醉大鼠中，通过上呼吸道（UA）/咽部扩张、使用von Frey细丝进行点状机械刺激、将辣椒素或蒸馏水（DW）局部应用于声带以及电刺激喉上神经（SLN）来诱发吞咽，并通过记录舌骨上肌和甲状舌骨肌的肌电图激活以及观察喉部抬高来记录。研究了每种药物腹腔内或局部给药对吞咽功能的影响。地西泮和巴氯芬全身给药可抑制机械、化学和电刺激诱发的吞咽，而美金刚或右美沙芬则无此作用。苯二氮䓬类药物和GABA受体拮抗剂均可减弱地西泮的抑制作用，而GABA受体拮抗剂可减弱巴氯芬的作用。局部应用地西泮或巴氯芬对吞咽无影响。这些数据表明，地西泮和巴氯芬在中枢发挥作用，抑制麻醉大鼠的吞咽。地西泮和巴氯芬全身给药可抑制机械、化学和电刺激诱发的吞咽，而美金刚或右美沙芬则无此作用。苯二氮䓬类药物和GABA受体拮抗剂均可减弱地西泮的抑制作用，而GABA受体拮抗剂可减弱巴氯芬的作用。局部应用地西泮或巴氯芬对吞咽无影响。地西泮和巴氯芬在中枢发挥作用，抑制麻醉大鼠的吞咽。
