Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant
Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant
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DOI：
10.1152/ajpgi.00197.2017
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发表时间：
2017-11-01
影响因子：
4.5
通讯作者：
Camilleri, Michael
中科院分区：
文献类型：
--
作者：
Jacob, Deepti;Busciglio, Irene;Camilleri, Michael
阿瑞匹坦是一种NK 1受体拮抗剂，通过阻断脑干呕吐中心的NK 1受体，被批准用于治疗化疗诱导或术后呕吐。NK 1受体对人类胃功能和餐后症状的影响尚不清楚;一项单交叉研究未显示阿瑞匹坦对胃肠道转运的显著影响。我们的目的是在一项随机、双盲、安慰剂对照、平行组研究中比较（每组12名健康志愿者），阿瑞匹坦与安慰剂对固体胃排空的影响（通过胃电描记术）320千卡的膳食，胃容量（GVs;禁食和调节（通过单光子发射计算机断层扫描），饱食[最大耐受量（MTV）]，和消化不良后的症状给予阿瑞匹坦（第1天125 mg，随后第2-5天80 mg）或安慰剂，每日一片，连续5天。统计学分析采用非配对秩和检验，校正性别差异和体重指数。为了评估治疗对症状的影响，我们将MTV纳入模型中。阿瑞匹坦增加空腹、餐后和调节GV，并倾向于增加充盈容量和MTV，增加幅度与200 kcal相似。然而，阿瑞匹坦在摄入Ensure的MTV后增加了综合症状、恶心和疼痛评分。阿瑞匹坦对固体胃半排空时间无显著影响。我们的结论是，NK 1受体参与GV的控制，并在确定餐后饱食和症状。NK 1受体拮抗剂在胃轻瘫和消化不良患者中的药效学和治疗作用的进一步研究是必要的。NEW & NOTEWORTHY阿瑞匹坦增加空腹，餐后和调节胃容量。阿瑞匹坦在营养饮料测试期间增加体积至充满度和最大耐受体积。NK 1受体参与胃容量的控制和确定餐后饱足感和症状。
Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs. placebo on gastric emptying of solids (by scintigraphy) with a 320-kcal meal, gastric volumes (GVs; fasting and accommodation by single photon emission-computed tomography), satiation [maximum tolerated volume (MTV)], and symptoms after a dyspeptogenic meal of Ensure. Aprepitant (125 mg on day 1, followed by 80 mg on days 2-5) or placebo, one tablet daily, was administered for 5 consecutive days. Statistical analysis was by unpaired rank sum test, adjusted for sex difference and body mass index. To assess treatment effects on symptoms, we incorporated MTV in the model. Aprepitant increased fasting, postprandial, and accommodation GV and tended to increase volume to fullness and MTV by similar to 200 kcal. However, aprepitant increased aggregate symptoms, nausea, and pain scores after ingestion the MTV of Ensure. There was no significant effect of aprepitant on gastric half-emptying time of solids. We conclude that NK1 receptors are involved in the control of GV and in determining postprandial satiation and symptoms. Further studies of the pharmacodynamics and therapeutic role of NK1 receptor antagonists in patients with gastroparesis and dyspepsia are warranted.NEW & NOTEWORTHYAprepitant increases fasting, postprandial, and accommodation gastric volumes. Aprepitant increases volume to fullness and maximum tolerated volume during a nutrient drink test. NK1 receptors are involved in the control of gastric volume and in determining postprandial satiation and symptoms.