GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man.
GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man.
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GR 38032F（昂丹司琼）是一种选择性 5HT3 受体拮抗剂，可减缓健康男性的结肠转运。
DOI：
10.1007/bf01536922
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发表时间：
1990
影响因子：
3.1
通讯作者：
Ciociola,A
中科院分区：
文献类型：
--
作者：
Talley,NJ;Phillips,SF;Haddad,A;Miller,LJ;Twomey,C;Zinsmeister,AR;MacCarty,RL;Ciociola,A
新认识的 5-羟色胺受体 (5HT3) 可能与恶心的诱发有关，因为它们的药理学拮抗剂可有效对抗化疗引起的呕吐。 5HT3受体存在于肠神经元上，5HT3阻滞剂可能会产生轻度便秘；因此，我们假设 5HT3 受体会调节结肠运动。为了确定 GR 38032F（一种已知具有止吐作用的选择性 5HT3 拮抗剂）是否影响健康的结肠转运，进行了一项随机、双盲、安慰剂对照的交叉研究。使用不透射线标记技术，对 39 名 18-70 岁健康志愿者（19 名男性，20 名非孕妇）的结肠转运进行了量化。在标准 25 克纤维饮食中，每天三次口服 16 毫克 GR 38032F。还在空腹和餐后血浆中测量胃肠肽（肽 YY、人胰多肽、神经降压素、胃动素、胃泌素胆囊收缩素、P 物质）。安慰剂组的平均总结肠传输时间为 27.8 小时，而 GR 38032F 组为 39.1 小时（P<0.0005）。该药物延长了通过左结肠（P<0.0005）和直肠乙状结肠（P<0.05）的转运时间，但右结肠转运没有显着改变。运输时间与年龄或性别无关，但运输时间较短的受试者比运输时间较长的受试者受到的影响明显更大。 GR 38032F后，肽YY的峰值释放略有下降（P<0.01），但人胰多肽、神经降压素、胃动素、胃泌素胆囊收缩素和P物质的峰值和积分餐后反应并未因该药物而显着改变。我们得出结论，5HT3 受体可能参与健康人结肠转运的调节。
The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3receptors are present on enteric neurons, and 5HT3blockers may produce mild constipation; we thus hypothesized that 5HT3receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P<0.0005). Transit times through the left colon (P<0.0005) and rectosigmoid (P<0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P<0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug. We conclude that 5HT3receptors may be involved in the regulation of colonic transit in healthy man.
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