Coffin B, Bouhassira D, Chollet R, Fraitag B, De Meynard C, Geneve J, Lemann M, Willer J C, Jian R
Service de Gastroentérologie Hôpital Saint-Louis, Paris, France.
Aliment Pharmacol Ther. 1996 Dec;10(6):919-25. doi: 10.1046/j.1365-2036.1996.109280000.x.
Gastric hypersensitivity to mechanical distension has been observed in functional dyspepsia, but no drug is available that specifically acts on gastric afferent pathways to decrease gastric nociception. The aim of this study was to assess the effect of fedotozine, a synthetic ligand for peripheral kappa receptors, on human gastric sensitivity.
Twenty-seven healthy volunteers were randomized to receive either fedotozine (30 mg t.d.s.) or a placebo, for 7 days. On day 7, the effects of fedotozine were tested on discomfort threshold and gastric compliance during graded isobaric and isovolumic distensions. In 16 of these subjects, the effect of this drug was tested on somatic sensitivity. In 10 other healthy volunteers the effect of fedotozine on gastric distension-induced inhibition of the RIII reflex, a process closely related to visceral sensitivity, was also studied.
During isobaric distensions, the discomfort threshold was significantly higher in subjects on fedotozine than in those on placebo (14.4 +/- 0.92 vs. 12.0 +/- 1.13 mmHg; P = 0.04). Compared to placebo, fedotozine did not modify gastric compliance and somatic sensitivity. Fedotozine also reduced the inhibition of the RIII reflex induced by gastric distension.
Fedotozine decreases gastric sensitivity to distension by exerting specific action on gastric afferent pathways.
在功能性消化不良患者中已观察到胃对机械扩张的超敏反应，但尚无专门作用于胃传入通路以降低胃伤害感受的药物。本研究旨在评估外周κ受体的合成配体非多托嗪对人体胃敏感性的影响。
27名健康志愿者被随机分为两组，分别接受非多托嗪（30毫克，每日三次）或安慰剂治疗，为期7天。在第7天，在分级等压和等容扩张过程中，测试非多托嗪对不适阈值和胃顺应性的影响。在其中16名受试者中，测试该药物对躯体敏感性的影响。在另外10名健康志愿者中，还研究了非多托嗪对胃扩张诱导的RIII反射抑制的影响，这一过程与内脏敏感性密切相关。
在等压扩张过程中，服用非多托嗪的受试者的不适阈值显著高于服用安慰剂的受试者（14.4±0.92对12.0±1.13毫米汞柱；P = 0.04）。与安慰剂相比，非多托嗪未改变胃顺应性和躯体敏感性。非多托嗪还减少了胃扩张诱导的RIII反射抑制。
非多托嗪通过对胃传入通路发挥特异性作用降低胃对扩张的敏感性。
