Morgan D R, Sellin J, Gutierrez L, DuPont H L, Wood L V
Infect Immun. 1985 Jun;48(3):754-8. doi: 10.1128/iai.48.3.754-758.1985.
BW942C, an enkephalin-like pentapeptide with anti-diarrheal activity, was tested against crude toxins of Escherichia coli and Vibrio cholerae in the Y-1 adrenal cell assay, rabbit ileal loop assay, and suckling mouse assay. The effects of BW942C on in vitro ion transport were measured in rabbit ileum mounted in Ussing chambers. In vitro, BW942C decreased basal short-circuit current (2.26 and 3.15 mueq cm-2 h-1 in experimental samples and controls, respectively; n = 7, P less than 0.05) and increased basal net Cl absorption (1.59 and 0.50 mueq cm-2 h-1 in experimental samples and controls, respectively; P less than 0.025). Net Na absorption was also increased, but not significantly. BW942C did not block the secretory response to a maximal dose of purified heat-stable toxin. BW942C directly enhanced intestinal fluid absorption. In the Y-1 adrenal cell assay, 5 mg of BW942C per ml inhibited the cytopathic effect caused by cholera toxin or heat-labile enterotoxin of E. coli. In the rabbit ileal loop assay, E. coli heat-stable toxin, E. coli heat-labile enterotoxin, and cholera toxin were inhibited 35 to 70% by administration of BW942C. With the suckling mouse model, the fluid accumulation caused by E. coli heat-stable toxin was ablated by prior treatment with BW942C. The drug is currently being evaluated in patients with acute secretory diarrhea to determine its effect on clinical symptoms.
BW942C是一种具有抗腹泻活性的脑啡肽样五肽，在Y-1肾上腺细胞试验、兔回肠袢试验和乳鼠试验中针对大肠杆菌和霍乱弧菌的粗毒素进行了测试。在安装于尤斯灌流小室中的兔回肠中测量了BW942C对体外离子转运的影响。在体外，BW942C降低了基础短路电流（实验样品和对照分别为2.26和3.15微当量·厘米-2·小时-1；n = 7，P<0.05），并增加了基础净氯吸收（实验样品和对照分别为1.59和0.50微当量·厘米-2·小时-1；P<0.025）。净钠吸收也增加了，但不显著。BW942C并未阻断对最大剂量纯化热稳定毒素的分泌反应。BW942C直接增强了肠液吸收。在Y-1肾上腺细胞试验中，每毫升5毫克的BW942C抑制了霍乱毒素或大肠杆菌热不稳定肠毒素引起的细胞病变效应。在兔回肠袢试验中，给予BW942C可使大肠杆菌热稳定毒素、大肠杆菌热不稳定肠毒素和霍乱毒素受到35%至70%的抑制。在乳鼠模型中，BW942C预先处理可消除大肠杆菌热稳定毒素引起的液体蓄积。目前正在对急性分泌性腹泻患者评估该药物，以确定其对临床症状的影响。
