Loperamide

In castor oil challenged rats, low doses of loperamide inhibit diarrhea and normalize intestinal propulsion. Unlike other opioids, loperamide is devoid of central opiate-like effects, including blockade of intestinal propulsion, up to the highest subtoxic oral dose. Nevertheless, the antidiarrheal action of loperamide can be considered to be -opiate receptor mediated, only a fewin vitro effects at rather high concentrations being not naloxone-reversible. There is little evidence that interactions with intestinal opiate receptors directly change epithelial cell function. When secretory stimuli increase mucosal tension, however, loperamide may reverse the elevated hydrostatic tissue pressure that opposes normal absorption. This antisecretory effect at the mucosal level is accompanied by motor effects when loperamide reaches the myenteric -opiate receptors. At therapeutic doses for the treatment of acute diarrhea, it is likely that the mucosal effect prevails.     

双苓止泻口服液治疗婴幼儿轮状病毒肠炎疗效观察

目的:评价双苓止泻口服液治疗小儿轮状病毒肠炎的疗效。方法:64例轮状病毒肠炎患儿随机分成双苓止泻口服液治疗组和常规治疗对照组。结果:治疗组和对照组总有效率分别为93.75％和87.5％,两组比较有显著性差异(P<0.05)。结论:双苓止泻口服液治疗小儿轮状病毒肠炎见效快,疗效肯定,不良反应少。     

Racecadotril versus loperamide: antidiarrheal research revisited

Racecadotril is an enkephalinase inhibitor, presented as a purely antisecretory agent with advantages over the opiate-receptor agonist loperamide in the treatment of diarrhea. A critical review of the literature and the models used was performed. Although pretreatment with high doses of racecadotril reduced cholera toxin-induced secretion and although clinical efficacy was demonstrated in young infants—a population characterized by 10-fold higher plasma enkephalin concentrations compared with adults, the analysis calls into question the peripheral antisecretory selectivity and relative clinical efficacy. Conversely, loperamide can be proposed as an antisecretory agent at therapeutic concentrations. Its efficacy is well established in acute and chronic diarrhea. Current experimental and clinical comparative studies of both drugs have problems with regard to the selection of the doses, the validity of models, and/or the trial design. The conclusion is that more research is needed before reliable conclusions can be drawn on the place of racecadotril in diarrhea treatment.     

基于盐炙前后成分煎出差异与止泻作用相关性探讨补骨脂丸增效机制

目的 探讨盐炙对补骨脂丸中代表性成分煎出的影响,以及成分与止泻药效的相关性。方法 采用HPLC-MS法测定补骨脂丸及3种补骨脂丸模拟品水煎液中13种代表性成分的含量差异,并结合不同给药组对脾肾阳虚泄泻模型大鼠的胃肠激素和下丘脑-垂体-肾上腺轴相关指标的影响,采用灰色关联分析法,对代表性成分与止泻药效进行相关性分析,寻找药效贡献较大成分。结果 与3种模拟品（模拟I～III号）相比,补骨脂丸水煎液中黄酮类成分如芦丁、异补骨脂二氢黄酮、新补骨脂异黄酮、补骨脂二氢黄酮、补骨脂宁、异补骨脂查耳酮及补骨脂二氢黄酮甲醚的含量较高,挥发油类成分如茴香醛、反式茴香脑及补骨脂酚的含量较低;与模拟II、III号相比,香豆素类成分如补骨脂素及异补骨脂素的含量较低。不同成分对止泻药效的贡献具有差异,黄酮类和挥发油类成分与止泻药效的关联度较高,香豆素类成分（如补骨脂素与异补骨脂素）与止泻药效的关联度较低。结论 补骨脂、小茴香盐炙后组成补骨脂丸,能促进黄酮类成分煎出,抑制挥发油类、香豆素类成分煎出,这可能是盐炙增强其止泻作用的关键环节之一。     

Lidamidine's effects on the lower gastrointestinal tract: A review

Lidamidine is a new, nonnarcotic, nonanticholinergic drug intended for the treatment of diarrhea. In preclinical test models, it compares favorably in both potency and duration of action with marketed antidiarrheal drugs. Lidamidine's intestinal antisecretory effects are mediated through the activation of peripheral alpha-2 adrenoceptors. Lidamidine crosses the blood brain barrier poorly and is therefore devoid of the centrally mediated alpha-2 effects that have limited the use of other alpha-2 adrenoceptor agonists in the intestinal tract. Lidamidine relaxes circular and longitudinal smooth muscle in the intestinal tract and may be useful for treatment of certain intestinal motility disorders. In clinical trials, lidamidine has proven to be effective for the management of diarrheal diseases.     

复方儿茶止泻液抗腹泻的药效学研究

目的通过对复方儿茶止泻液配伍前后进行小鼠抗腹泻药效学实验,探讨其作用机理。方法建立小鼠腹泻模型,进行抗腹泻的药效学实验,考察复方儿茶止泻液的抗腹泻效果。结果 大黄所致小鼠腹泻次数与生理盐水组比较:复方儿茶止泻液2 g/kg和4 g/kg组与盐酸小檗碱阳性对照组在1～2 h有非常显著性差异(P<0.01),复方儿茶止泻液4 g/kg组作用效果优于2 g/kg组;儿茶提取液4 g/kg组在1～4 h有显著性差异(P<0.05);黄柏提取液4 g/kg组在1～2 h有显著性差异(P<0.05);五倍子提取液2 g/kg组在1～2 h有显著性差异(P<0.05),4 g/kg组在1～3 h有显著性差异(P<0.05);木香提取液4 g/kg组在1 h有显著性差异(P<0.05)。胃肠推进率与生理盐水组比较:硫酸阿托品阳性对照组、复方儿茶止泻液2 g/kg和4 g/kg组、五倍子提取液4 g/kg组的胃肠推进率有非常显著性差异(P<0.01);儿茶提取液、黄柏提取液、木香提取液4g/kg组的胃肠推进率有显著性差异(P<0.05)。结论 复方儿茶止泻液能更加显著地抑制小鼠胃肠推进速度,具有较强并且持久的抗腹泻作用。提示该制剂组方综合抗腹泻的有效活性成分增多,对其药效物质基础有待于进一步深入研究。     

Species Differences in the Antidiarrheal and Antispasmodic Activities of Lepidium sativum and Insight into Underlying Mechanisms

The aim of this study was to see if the crude extract of Lepidium sativum (Ls.Cr) exhibits species specificity in its antidiarrheal and antispasmodic activities along with insight into the underlying mechanisms using the in‐vivo and in‐vitro experiments. Ls.Cr inhibited castor oil‐induced diarrhea in mice at doses (300 and 1000 mg/kg) three times higher dose than for rats. In isolated rat ileum and jejunum, Ls.Cr completely inhibited carbachol (CCh), low K⁺ (25 mM) and high K⁺ (80 mM)‐induced contractions, while in guinea‐pig tissues, Ls.Cr caused complete inhibition of only CCh‐induced contraction. In rabbit tissues, Ls.Cr completely inhibited CCh and low K⁺‐induced contractions sensitive to K⁺ channel antagonists. Pretreatment of guinea‐pig and rat tissues with Ls.Cr caused a rightward shift in CCh‐induced contractions in a pattern similar to dicyclomine, while in rabbit and rat tissues, Ls.Cr shifted isoprenaline curves to the left similar to papaverine. These data indicate that the antidiarrheal and antispasmodic activities of L. sativum are species dependent, mediating its antispasmodic effect through combinations of multiple pathways including activation of K⁺ channels, and inhibition of muscarinic receptors, Ca⁺⁺ channels and PDE enzyme. Rat tissues showed the highest potency. Based on the results, we recommend using multiple species to know the real pharmacological profile of medicinal products. Copyright © 2012 John Wiley & Sons, Ltd.     

Safety and Efficacy of Bixa orellana (Achiote,Annatto) Leaf Extracts

Bixa orellana leaf preparations have been used for many years by indigenous people for a variety of medicinal applications. Published research studies in animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad antimicrobial (antibacterial and antifungal), anti‐inflammatory, analgesic, hypoglycemic, and antidiarrheal activities. No studies have specifically assessed the ability of leaf extracts to inhibit urogenital infections although Bixa products have been used in folkloric medicine to treat gonorrhea and other infections. Few human studies have been conducted and published using Bixa leaf preparations. Many more studies have been conducted and published involving Bixa seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity) studies have been conducted in animals. A 6 month study in humans given 750 mg of leaf powder per day demonstrated no significant or serious adverse effects. Bixa leaf extracts appear to be safe when given under current conditions of use. However, additional human and animal controlled safety and efficacy studies are needed. In addition, detailed chemical analyses are required to establish structure–function relationships. Copyright © 2013 John Wiley & Sons, Ltd.     

Antidiarrheal and antiulcer activity of Amaranthus spinosus in experimental animals

The ethanol extract (50%) of the whole plant of Amaranthus spinosus Linn. (Amaranthaceae) (ASE) significantly inhibited travel of a charcoal meal at three different doses of ASE, but when 400?mg/kg of ASE was repeated in the presence of yohimbine, intestinal propulsive inhibition decreased, while morphine reversed the activity. The percentages related to controls for the onset of diarrhea were 16.58, 83.42, and 116.18% at doses of 100, 200, and 400?mg/kg of ASE, while with morphine this value was 123.93% compared to controls. The percentage purging frequency related to controls was 41.09, 64.38, 71.23, and 86.30% at three different doses of ASE and with morphine, respectively. The inhibitions in intestinal accumulation were 8.9, 48.16, and 68.06% at doses of 100, 200, and 400?mg/kg of ASE, respectively, compared to control, while inhibition with yohimbine was 50.78%. Antidiarraheal indices of ASE were 23.55, 49.16, and 76.53 at the three different doses of ASE, while morphine had a maximum index of 88.45. Protection in ethanol- induced ulcer was 51.07, 55.91, 77.95, and 60.75%, but in aspirin-induced ulcer it was 41.33, 61.77, 80.88, and 74.66% at doses of 100, 200, and 400?mg/kg of ASE and with cimetidine, respectively. Lipid peroxidation was also associated with a concomitant decrease in ulcer index, while protection was 56.96, 63.29, 81.01, and 52.32% at three different doses of ASE and with cimetidine in cold restraint-induced ulcer.     

Studies on antidiarrheal and antispasmodic activities of Lepidium sativum crude extract in rats

This study was aimed to provide the pharmacological basis for the medicinal use of Lepidium sativum in diarrhea using in vivo and in vitro assays. The seed extract of Lepidium sativum (Ls.Cr) at 100 and 300 mg/kg inhibited castor oil‐induced diarrhea in rats. In isolated rat ileum, Ls.Cr (0.01–5 mg/mL) reversed carbachol (CCh, 1 µ m ) and K⁺ (80 m m )‐induced contractions with higher potency against CCh, similar to dicyclomine. Preincubation of rat ileum with a lower concentration of Ls.Cr (0.03 mg/mL) caused a rightward parallel shift in the concentration–response curves (CRCs) of CCh without suppression of the maximum response, while at the next higher concentration (0.1 mg/mL), it produced a non‐parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine. Ls.Cr shifted the CRCs of Ca⁺⁺ to the right with suppression of the maximum response, similar to verapamil. These data suggest that Lepidium sativum seed extract possesses antidiarrheal and spasmolytic activities mediated possibly through dual blockade of muscarinic receptors and Ca⁺⁺ channels, though additional mechanism(s) cannot be ruled out and this study explains its medicinal use in diarrhea and abdominal cramps. Copyright © 2011 John Wiley & Sons, Ltd.