Assessment of Cevimeline Effects on Isolated Rat's Tracheal Smooth Muscle

評估cevimeline對於離體老鼠氣管平滑肌之作用

林原永(Yuan-Yung Lin) ； 賴文森(Wen-Sen Lai) ； 鄭立享(Li-Hsiang Cheng) ； 劉紹正(Shao-Cheng Liu) ； 邱逢翔(Feng-Hsiang Chiu) ； 朱永祥(Yueng-Hsiang Chu) ； 王興萬(Hsing-Won Wang)

《台灣耳鼻喉頭頸外科雜誌》 54卷1期 (2019/03) Pp. 10-16

https://doi.org/10.6286/jtohns.201903_54(1).10

摘要

BACKGROUND: Cevimeline is a muscarinic receptor agonist and is approved in the United States for the symptomatic treatment of xerostomia associated with Sjögren's syndrome. The effect of cevimeline on the trachea is an issue worthy of investigation because when topical use by oral gargling or spraying, the trachea may be affected. METHOD: To verify the effect of cevimeline, which acts on the tracheal smooth muscle directly in vitro, we used our preparation to test the effects of cevimeline on isolated rat's tracheal smooth muscle. The following assessments of cevimeline were performed: (1) effect on the tracheal smooth muscle resting tension, (2) effect on contraction caused by 10^(-6) M methacholine as a parasympathetic mimetic, and (3) effect of the drugs on electrically induced tracheal smooth muscle contractions. RESULT: The results indicated that the addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of cevimeline at doses of 10^(-6) M or above elicited a significant relaxation response to 10^(-6) M methacholine-induced contraction. Cevimeline could not inhibit or enhance electrical field stimulation induced spike contraction. It also had a minimal effect on the basal tension of trachea as the concentration increased. CONCLUSION: This study indicated that high concentrations of cevimeline might have an anti-cholinergic effect of the trachea. Cevimeline might partially reduce the degree of asthma attack when administered to patients with xerostomia because it could reduce methacholine-induced contraction of tracheal smooth muscle.

關鍵字

Cevimeline ； Trachea ； Smooth muscle ； In vitro study

並列摘要

背景：西維美林（cevimeline）為一種蕈鹼類受器促效劑（muscarinic agonist），在美國被證實可用於治療乾燥症導致的口乾。由於當口乾症患者以漱口或是噴灑方式於口腔局部使用西維美林藥物時，此藥亦有可能會直接影響氣管，而本實驗的目的，即在於探討西維美林直接作用於老鼠離體氣管後的效應。方法：本實驗測試加入西維美林藥物於離體老鼠氣管後，其氣管組織張力變化情形，實驗評估方式主要分成3組：（1）由低到高依序將不同濃度的西維美林加入溶液裡，測試其對氣管基礎張力的影響變化；（2）先於溶液裡加入10^(-6)M乙醯甲膽鹼（methacholine）使氣管收縮，再由低到高依序加入不同濃度的西維美林；（3）以電刺激使氣管收縮，再由低到高依序加入不同濃度的西維美林；上述實驗在給予藥物後記錄其氣管張力變化。結果：當氣管因乙醯甲膽鹼（methacholine）收縮後，較高濃度的西維美林（10^(-6)M－10^(-4)M）會降低氣管的張力，使其舒張。但不同濃度的西維美林不影響氣管因電刺激造成的張力增加。單獨添加西維美林對於氣管張力幾乎沒有改變。結論：高濃度的西維美林可拮抗乙醯甲膽鹼（methacholine）的膽鹼性收縮，當口乾症病人使用西維美林時，有可能可以減少氣喘發作時氣管收縮的程度。

並列關鍵字

Cevimeline ； Trachea ； Smooth muscle ； In vitro study（西維美林 ； 氣管 ； 平滑肌 ； 離體試驗）