BACKGROUND & AIMS: :Gaze-stabilization exercise (GSE) is often conducted in vestibular rehabilitation, but its effect on vestibular function in postural control is not clear. We investigated whether GSE affects vestibular function during static upright standing and vestibulospinal reflex (VSR) in healthy young adults. First, the center of pressure of the total trajectory length (CoP-L) was measured before each GSE task or control (only standing) task (pre), immediately after (post), and 10 min after (post10) in the static standing position on foam rubber with the eyes open or closed (EC). Second, the H-reflex on the soleus muscle was measured after the onset of ipsilateral anodal galvanic vestibular stimulation before and after a GSE or a control task to estimate the amount of VSR induced by electrical vestibular input. CoP-L for the pre, post, and post10 control tasks and the GSE in EC did not differ significantly; the CoP-L for the post and post10 tasks in EC were significantly lower than that for the pretask. The H-reflex was inhibited by galvanic vestibular stimulation in the pre-GSE tasks. The inhibition increased after GSE, but not during control tasks. These findings suggest that GSE immediately improves the postural stability required for vestibular function and can be mediated by VSR improvements.

背景与目标： ：凝视稳定运动（GSE）通常在前庭康复中进行，但对姿势控制中前庭功能的影响尚不清楚。我们调查了健康年轻人在静态直立站立和前庭脊髓反射（VSR）期间，GSE是否会影响前庭功能。首先，在静态站立时，在每个GSE任务或控制（仅站立）任务（前）之前，之后（后）和之后（post10）之后的10分钟内，测量总轨迹长度（CoP-L）的压力中心睁眼或闭眼（EC）将其放在泡沫橡胶上。其次，在GSE或控制任务之前和之后，在同侧肛门电流前庭刺激开始后，测量比目鱼肌的H反射，以估计由前庭电输入引起的VSR量。前，后和后10个控制任务的CoP-L与EC中的GSE并无显着差异。 EC中的post和post10任务的CoP-L显着低于pretask的CoP-L。 GSE之前的任务中，前庭电刺激抑制了H反射。抑制作用在GSE后增加，但在控制任务期间没有增加。这些发现表明，GSE可立即改善前庭功能所需的姿势稳定性，并可通过VSR的改善来介导。

BACKGROUND & AIMS:

背景与目标：

BACKGROUND & AIMS: :Domperidone and Itopride are pro-kinetic agents, regulating the gastric motility and are commonly prescribed as anti emetic drugs. In the present study a simple, rapid and sensitive RP-HPLC/UV method was developed for simultaneous determination of Domperidone and Itopride in pharmaceutical samples and human plasma, using Tenofavir as internal standard. Experimental conditions were optimized and method was validated according to the standard guidelines. Combination of water (pH 3.0) and acetonitrile (65:35 v/v) was used as mobile phase, pumped at the flow rate of 1.5 ml/min. Detector wavelength was set at 210 nm and column oven temperature was 40oC. Unlike conventional liquid-liquid extraction, simple precipitation technique was applied for drug extraction from human plasma using acetonitrile for deprotienation. The method showed adequate separation of both the analytes and best resolution was achieved using Hypersil BDS C8 column (150 mm × 4.6 mm, 5 μm). The method was quite linear in the range of 20-600 ng/ml. Recovery of the method was 92.31% and 89.82% for Domperidone and Itopride, respectively. Retention time of both the analytes and internal standard was below 15 min. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for Domperidone were 5 and 10 ng/ml while for Itopride was 12 and 15 ng/ml, respectively. The developed method was successfully applied for in-vivo analysis of fast dispersible tablets of Domperidone in healthy human volunteer. The proposed method was a part of formulation development study and was efficiently applied for determination of the two drugs in various pharmaceutical products and human plasma.

背景与目标： 多潘立酮和伊托必利是促动剂，可调节胃动力，通常被处方为催吐药。在本研究中，开发了一种简单，快速，灵敏的RP-HPLC / UV方法，以替诺福韦作为内标，同时测定药物样品和人血浆中的多潘立酮和伊托必利。根据标准指南优化了实验条件并验证了方法。将水（pH 3.0）和乙腈（65:35 v / v）的混合物用作流动相，以1.5 ml / min的流速泵送。检测器波长设置为210 nm，柱温箱温度为40oC。与常规液-液萃取不同，简单的沉淀技术被应用于使用乙腈脱去质从人血浆中提取药物。该方法显示了两种分析物的充分分离，使用Hypersil BDS C8色谱柱（150 mm×4.6 mm，5μm）可实现最佳分离度。该方法在20-600 ng / ml范围内呈线性。多潘立酮和伊托必利的方法回收率分别为92.31％和89.82％。分析物和内标物的保留时间均在15分钟以下。多潘立酮的检测下限（LLOD）和定量下限（LLOQ）分别为5和10 ng / ml，而伊托必利的分别为12和15 ng / ml。所开发的方法已成功地用于健康人志愿者中多潘立酮快速分散片的体内分析。所提出的方法是制剂开发研究的一部分，可有效地用于测定各种药品和人体血浆中的两种药物。

BACKGROUND & AIMS:

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with anti-acetylcholinesterase [corrected] effects, in patients with functional dyspepsia. METHODS:Patients with functional dyspepsia were randomly assigned to receive either itopride (50, 100, or 200 mg three times daily) or placebo. After eight weeks of treatment, three primary efficacy end points were analyzed: the change from baseline in the severity of symptoms of functional dyspepsia (as assessed by the Leeds Dyspepsia Questionnaire), patients' global assessment of efficacy (the proportion of patients without symptoms or with marked improvement), and the severity of pain or fullness as rated on a five-grade scale. RESULTS:We randomly assigned 554 patients; 523 had outcome data and could be included in the analyses. After eight weeks, 41 percent of the patients receiving placebo were symptom-free or had marked improvement, as compared with 57 percent, 59 percent, and 64 percent receiving itopride at a dose of 50, 100, or 200 mg three times daily, respectively (P<0.05 for all comparisons between placebo and itopride). Although the symptom score improved significantly in all four groups, an overall analysis revealed that itopride was significantly superior to placebo, with the greatest symptom-score improvement in the 100- and 200-mg groups (-6.24 and -6.27, vs. -4.50 in the placebo group; P=0.05). Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo (73 percent vs. 63 percent, P=0.04). CONCLUSIONS:Itopride significantly improves symptoms in patients with functional dyspepsia. (ClinicalTrials.gov number, NCT00272103.).

背景与目标： 背景：功能性消化不良患者的治疗仍不令人满意。我们评估了伊托必利（一种具有抗乙酰胆碱酯酶[校正]作用的多巴胺D2拮抗剂）在功能性消化不良患者中的疗效。
方法：将具有功能性消化不良的患者随机分配为接受伊托必利（每日3次，每次50、100或200毫克）或安慰剂。在治疗八周后，分析了三个主要功效终点：功能性消化不良症状严重程度相对于基线的变化（由利兹消化不良问卷评估），整体疗效评估（无症状或无症状的患者比例）有明显改善），以及疼痛或饱胀的严重程度（以五级量表评分）。
结果：我们随机分配了554例患者。 523有结果数据，可以纳入分析。八周后，接受安慰剂的患者中有41％无症状或有明显改善，而分别以50、100或200 mg的剂量每天3次接受伊托必利的患者分别为57％，59％和64％。 （对于安慰剂和伊托必利之间的所有比较，P <0.05）。尽管在所有四个组中症状评分均显着改善，但总体分析显示，伊托必利明显优于安慰剂，在100和200 mg组中，症状评分改善最大（-6.24和-6.27，而-4.50在安慰剂组中； P ＝ 0.05）。对疼痛和饱胀感综合终点的分析表明，伊托必利产生的反应率高于安慰剂（73％vs. 63％，P = 0.04）。
结论：依托必利可显着改善功能性消化不良患者的症状。 （ClinicalTrials.gov编号，NCT00272103。）。

BACKGROUND & AIMS: :Several methods are used to evaluate gastric motility in rodents, but they all have technical limitations. Recent technical developments enable a convenient method to evaluate gastric motility. The (13)C-acetic acid breath test in rodents is a non-invasive and repeatable method that can be used without physical restraints. The present study aimed to validate the (13)C-acetic acid breath test by measuring the effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice. Loperamide (1-10 mg/kg) and morphine (1.25-10 mg/kg) slowed gastric emptying and decreased the maximum concentration (C(max)) and area under the curve (AUC(90 min)) value in a dose-dependent manner. Mosapride (0.2-5 mg/kg) accelerated gastric emptying and increased C(max) value. Mosapride (20 mg/kg) did not accelerate gastric emptying on the (13)C-breath test. Itopride (30 mg/kg, per os) significantly accelerated gastric emptying compared with the vehicle group. In a comparison with the conventional phenol red test, there was a correlation between the C(max) value of breath test and gastric emptying (%) of phenol red tests in treatment with loperamide or mosapride. These results indicate that the (13)C-acetic acid breath test is an accurate, noninvasive, and simple method for monitoring gastric emptying in mice. This method is useful to assess the effect of drugs and gut function pharmacologically.

背景与目标： ：有几种方法可用于评估啮齿动物的胃动力，但是它们都有技术上的局限性。最近的技术发展为评估胃动力提供了一种方便的方法。啮齿动物的（13）C-乙酸呼气试验是一种无创且可重复的方法，可以在没有物理限制的情况下使用。本研究旨在通过测量洛哌丁胺，吗啡，莫沙必利和伊托必利对小鼠胃排空的影响来验证（13）C-乙酸呼气试验。剂量下的洛哌丁胺（1-10 mg / kg）和吗啡（1.25-10 mg / kg）减慢了胃排空速度，降低了最大浓度（C（max））和曲线下面积（AUC（90 min））值-依赖方式。莫沙必利（0.2-5 mg / kg）加速胃排空并增加C（max）值。莫沙必利（20 mg / kg）在（13）C呼气试验中并未加速胃排空。与媒介物组相比，依托必利（30 mg / kg，口服）显着加速了胃排空。与常规酚红试验比较，在用洛哌丁胺或莫沙必利治疗时，呼气试验的C（max）值与酚红试验的胃排空率（％）之间存在相关性。这些结果表明，（13）C-乙酸呼气试验是一种监测小鼠胃排空的准确，无创且简单的方法。此方法可用于从药理学角度评估药物的作用和肠道功能。

BACKGROUND & AIMS: :The goals of the present study were to identify the enzyme responsible for metabolism of itopride hydrochloride (itopride) and to evaluate the likelihood of drug interaction involving itopride. In human liver microsomes, the involvement of flavin-containing monooxygenase in N-oxygenation, the major metabolic pathway of itopride, was indicated by the following results: inhibition by methimazole and thiourea, heat inactivation, and protection against heat inactivation by NADPH. When the effects of ketoconazole on the metabolism of itopride, cisapride, and mosapride citrate (mosapride) were examined using human liver microsomes, ketoconazole strongly inhibited the formation of the primary metabolites of cisapride and mosapride, but not itopride. Other cytochrome P450 (CYP) 3A4 inhibitors, cimetidine, erythromycin, and clarithromycin, also inhibited the metabolism of cisapride and mosapride. In an in vivo study, itopride (30 mg/kg), cisapride (1.5 mg/kg), or mosapride (3 mg/kg) was orally administered to male rats with or without oral pretreatment with ketoconazole (120 mg/kg) twice daily for 2 days. The ketoconazole pretreatment significantly increased the area under the serum concentration curve and the maximum serum concentration of cisapride and mosapride but had no significant effect on the pharmacokinetics of itopride. In addition, itopride did not inhibit five specific CYP-mediated reactions of human liver microsomes. These results suggest that itopride is unlikely to alter the pharmacokinetics of other concomitantly administered drugs.

背景与目标： ：本研究的目的是鉴定负责盐酸伊托必利（伊托必利）代谢的酶，并评估涉及伊托必利的药物相互作用的可能性。在人类肝脏微粒体中，下列结果表明了含黄素的单加氧酶参与了伊托必利的主要代谢途径N-加氧：甲巯咪唑和硫脲的抑制作用，热失活以及NADPH防止热失活的作用。当使用人肝微粒体检查酮康唑对伊托必利，西沙必利和柠檬酸莫沙必利（莫沙必利）代谢的影响时，酮康唑强烈抑制西沙必利和莫沙必利的主要代谢物的形成，但不能抑制伊托必利。其他细胞色素P450（CYP）3A4抑制剂西咪替丁，红霉素和克拉霉素也抑制西沙必利和莫沙必利的代谢。在一项体内研究中，对雄性大鼠口服给予伊托必利（30 mg / kg），西沙必利（1.5 mg / kg）或莫沙必利（3 mg / kg），口服或不口服酮康唑（120 mg / kg）两次每天2天。酮康唑预处理显着增加了血药浓度曲线下的面积以及西沙必利和莫沙必利的最大血药浓度，但对伊托必利的药代动力学没有显着影响。此外，伊托必利不抑制人肝微粒体的五种特定的CYP介导的反应。这些结果表明伊托必利不太可能改变其他同时给药药物的药代动力学。

BACKGROUND & AIMS:

背景与目标：

BACKGROUND & AIMS: BACKGROUND:To date, no definitive treatment of functional dyspepsia (FD) has been proven to be effective and reasonably well-tolerated. Proton pump inhibitors (PPIs) combined with prokinetic agents are considered an effective option. Revaprazan is a selective potassium-competitive acid blocker that reversibly inhibits gastric H(+)/K(+)-ATPase and shows effective acid suppression comparable to PPIs. Itopride is a prokinetic agent that has anticholinesterase activity as well as dopamine D(2) receptor antagonistic activity. For this reason, revaprazan and itopride have been prescribed for FD; however, no available studies have reported the pharmacokinetic interactions of these 2 drugs. OBJECTIVE:The objective of this study was to compare the bioavailability and tolerability of revaprazan and itopride combination therapy to those of equally dosed monotherapies to acquire basic drug-drug interaction information about revaprazan. METHODS:This multiple-dose, randomized crossover study was conducted in healthy male Korean subjects. Subjects received, in randomized sequence, a 7-day oral dose of revaprazan 200 mg once daily, itopride 50 mg TID, or both. Each treatment period was separated by a 7-day washout period. Blood samples were collected for up to 24 hours following the last dose at steady state, and drug concentrations were determined using validated LC/MS-MS. Pharmacokinetic properties were obtained using noncompartmental analysis. Drug tolerability was assessed throughout the study, using measurements of vital signs, clinical chemistry testing, and interviews. RESULTS:A total of 30 subjects were enrolled in the study. Among them, 28 subjects completed revaprazan treatment, and 27 completed the study (3 subjects were withdrawn). The geometric mean ratios (GMRs) (90% CI) of C(max,ss), and AUC(τ,ss) with revaprazan were 0.92 (0.84-1.00) and 0.96 (0.89-1.03), respectively. The GMRs of C(max,ss) and AUC(τ,ss) with itopride were 1.07 (0.96-1.20) and 1.12 (1.06-1.18), respectively. A total of 15 adverse events (AEs) were reported in 8 subjects. All AEs were considered to be mild, and there were no clinically significant differences between treatment groups. CONCLUSION:The findings from this study suggest bioequivalence between revaprazan given as monotherapy and in combination with itopride in these healthy Korean male volunteers, with no clinical significant drug-drug interaction. All treatments in this study was generally well tolerated. ClinicalTrials.gov identifier: NCT0133289.

背景与目标： 背景：迄今为止，尚无权威的功能性消化不良（FD）治疗方法被证明是有效且耐受性良好的。质子泵抑制剂（PPI）与促动力剂结合被认为是有效的选择。 Revaprazan是一种选择性钾竞争性酸阻滞剂，可逆地抑制胃H（）/ K（）-ATPase，并显示出与PPI相当的有效酸抑制作用。依托必利是一种具有抗胆碱酯酶活性以及多巴胺D（2）受体拮抗活性的促动力剂。因此，已为FD规定了瑞伐拉赞和伊托必利。但是，尚无可用的研究报道这两种药物的药代动力学相互作用。
目的：本研究的目的是比较瑞伐拉赞和伊托必利联合疗法与等剂量单药疗法的生物利用度和耐受性，以获取有关瑞伐拉赞的基本药物相互作用信息。
方法：这项多剂量，随机交叉研究是在健康的韩国男性受试者中进行的。受试者随机接受7天口服瑞伐拉赞200毫克/天，伊托必利50毫克TID或两者兼有。每个治疗期间隔7天的清除期。在稳定状态下最后一次给药后长达24小时内收集血样，并使用经过验证的LC / MS-MS确定药物浓度。使用非房室分析获得药代动力学性质。在整个研究过程中，使用生命体征的测量，临床化学测试和访谈对药物耐受性进行了评估。
结果：总共30名受试者参加了该研究。其中，有28位受试者完成了瑞伐拉赞治疗，还有27位受试者完成了研究（退出了3位受试者）。 C（max，ss）和AUC（τ，ss）与瑞伐拉赞的几何平均比（GMR）（90％CI）分别为0.92（0.84-1.00）和0.96（0.89-1.03）。带有伊托必利的C（max，ss）和AUC（τ，ss）的GMR分别为1.07（0.96-1.20）和1.12（1.06-1.18）。在8位受试者中总共报告了15次不良事件（AE）。所有不良事件均被视为轻度，治疗组之间在临床上无显着差异。
结论：这项研究的结果表明，在这些健康的韩国男性志愿者中，瑞伐拉赞单药治疗与伊托必利联用具有生物等效性，且无临床上显着的药物相互作用。这项研究中的所有治疗方法一般都耐受良好。 ClinicalTrials.gov标识符：NCT0133289。

BACKGROUND & AIMS: AIM:To evaluate the therapeutic effects of itopride vs other drugs (placebo, domperidone, mosapride) for functional dyspepsia (FD). METHODS:Randomized controlled trials (RCTs) of itopride for FD were retrieved from databases. Relevant information was extracted and analyzed, using the relative risk (RR) and weighted mean deviation, as appropriate. A random or fixed effect model was used, based on the heterogeneity of the included articles, and visual inspection of funnel plots was used to evaluate publication bias. RESULTS:Nine RCTs enrolling 2620 FD cases were included; 1372 cases received itopride treatment and 1248 cases received placebo or other drugs (control groups). Compared with control groups, itopride had superior RR values of 1.11 [95%CI: (1.03, 1.19), P = 0.006], 1.21 [95%CI: (1.03, 1.44), P = 0.02], and 1.24 [95%CI: (1.01, 1.53), P = 0.04] for global patient assessment, postprandial fullness, and early satiety, respectively. For the Leeds Dyspepsia Questionnaire score, the weighted mean deviation was -1.38 [95%CI: (-1.75, -1.01), P < 0.01]. The incidence of adverse effects was similar in the itopride and control groups. The funnel plots for all indicators showed no evidence of publication bias. CONCLUSION:Itopride has good efficacy in terms of global patients assessment, postprandial fullness, and early satiety in the treatment of patients with FD and shows a low rate of adverse reactions. Itopride can greatly improve FD syndromes-score.

背景与目标： 目的：评估伊托必利与其他药物（安慰剂，多潘立酮，莫沙必利）对功能性消化不良（FD）的治疗效果。
方法：从数据库中检索伊托必利用于FD的随机对照试验（RCT）。适当地使用相对风险（RR）和加权平均偏差来提取和分析相关信息。基于所包含文章的异质性，使用了随机或固定效应模型，并且使用漏斗图的目测检查来评估发布偏差。
结果：共纳入9例RCT，共纳入2620例FD病例。接受伊托必利治疗的患者为1372例，接受安慰剂或其他药物的患者为1248例（对照组）。与对照组相比，伊托必利具有较高的RR值，分别为1.11 [95％CI：（1.03，1.19），P = 0.006]，1.21 [95％CI：（1.03，1.44），P = 0.02]和1.24 [95％ CI：（1.01，1.53），P = 0.04]分别用于总体患者评估，餐后饱腹感和早期饱腹感。对于利兹消化不良调查问卷评分，加权平均偏差为-1.38 [95％CI：（-1.75，-1.01），P <0.01]。在伊托必利和对照组中，不良反应的发生率相似。所有指标的漏斗图均未显示出版偏倚的证据。
结论：依托必利在FD患者的整体患者评估，餐后饱胀和早饱方面均具有良好的疗效，不良反应发生率低。依托必利可大大改善FD综合征评分。

BACKGROUND & AIMS:

背景与目标：

BACKGROUND & AIMS: BACKGROUND/AIMS:Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. METHODS:Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. RESULTS:We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. CONCLUSIONS:DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety.

背景与目标： 背景/目的：功能性消化不良（FD）的治疗是有限的。 DA-9701是一种新型的促运动剂，由咽炎精液和延胡索块茎制成。我们旨在评估DA-9701与伊托必利在FD患者中的疗效。
方法：FD患者在基线期2周后随机接受伊托必利50 mg或DA-9701 30 mg t.i.d.治疗4周后，分析了2个主要功效终点：8个消化不良症状的综合评分与基线相比的变化以及总体治疗效果。使用尼泊尔消化不良指数（NDI）问卷评估了对患者生活质量的影响。
结果：我们随机分配了464例患者和455例具有结果数据的患者。两组之间的8个症状的综合评分变化的差异为0.62，表明DA-9701不逊于伊托必利。两组之间的总体治疗效果反应率无差异。当将应答者定义为7李克特量表中的≥5时，应答率是DA-9701的37％和伊托必利组的36％。与接受伊托必利治疗的患者相比，接受DA-9701治疗的患者在4周的治疗期内平均可缓解的天数百分比相似（56.8％vs 59.1％）。两种药物均增加了5个域的NDI评分，两组之间的NDI评分变化没有任何差异。两种药物的安全性均具有可比性。
结论：DA-9701可显着改善FD患者的症状。 DA-9701显示出与伊托必利同等的安全性，且疗效不逊于伊托必利。

BACKGROUND & AIMS: PURPOSE:Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS:The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10 cm with 2-cm intervals. RESULTS:In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6) M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9) M). Dopamine (10(-8) M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6) M). Dopamine (10(-8) M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION:Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.

背景与目标： 用途：盐酸依托必利（itopride）抑制乙酰胆碱酯酶（AChE）并拮抗多巴胺D（2）受体，并已被用作胃肠动力药。然而，其对小肠或结肠的促动力作用尚未得到充分研究。这项研究的目的是调查伊托必利对豚鼠回肠和结肠运动功能的影响。
材料与方法：切除回肠远端，通过测量蠕动收缩的幅度和传播速度来确定蠕动收缩的活动。移除远端结肠，并连接至包含克雷布斯-亨塞利特溶液（K-H溶液）的腔室。将人造粪便插入管腔的口腔侧，并通过蠕动泵通过腔内灌注向肛门侧移动。通过人造粪便以2 cm的间隔移动总长度10 cm所需的时间来测量结肠的转运时间。
结果：在回肠中，伊托必利以较高的剂量（10（-10）-10（-6）M）加速蠕动速度，而新斯的明仅以较低的剂量（10（-10）-10（-9）M）加速蠕动速度。 。多巴胺（10（-8）M）降低了通过伊托必利输液恢复的速度。更高剂量（10（-10）-10（-6）M）时，伊托必利和新斯的明可显着缩短结肠转运。多巴胺（10（-8）M）延迟了结肠运输时间，在输注伊托必利后也得以恢复。
结论：依托必利对回肠和结肠均具有促运动作用，这通过对AChE的抑制作用和对多巴胺D（2）受体的拮抗作用来调节。

BACKGROUND & AIMS: :Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.

背景与目标： ：盐酸异托必利（itopride）是一种胃肠动力药物，最近已评估其在功能性消化不良中的临床实用性。我们研究了伊托必利对人血浆胃泌素，生长抑素，胃动素和胆囊收缩素（CCK）样免疫反应物质（IS）的影响；健康受试者在应激条件下的促肾上腺皮质激素（ACTH）-免疫反应性物质（IS）和皮质醇。与安慰剂相比，单次服用伊托必利会导致血浆生长抑素和胃动素-IS水平显着增加。与安慰剂相比，依托必利显着降低血浆CCK-IS，并抑制ACTH-IS水平。我们假设伊托必利可能具有加速胃排空的作用，并对下丘脑-垂体-肾上腺轴和植物神经功能有调节作用。这些作用可能在与压力有关的疾病中是有益的，表明伊托必利具有临床药理活性。

BACKGROUND & AIMS: :We investigated the effects of itopride hydrochloride (itopride, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, on the colonic motor activity in vitro and in vivo, in comparison with benzamides, cisapride hydrate (cisapride), and mosapride citrate (mosapride). Itopride stimulated both peristaltic and segmental motility induced by applying intraluminal pressure to the isolated guinea pig colon. Although cisapride and mosapride enhanced the segmental motility, they markedly reduced the peristaltic motility. In conscious dogs with implanted strain gauge force transducers, itopride stimulated contractile activity in the gastrointestinal tract from the stomach to the colon. Cisapride stimulated contractile activity in the gastric antrum, ileum, and ascending colon. Mosapride stimulated contractile activity only in the gastric antrum and ileum. In guinea pigs and rats, itopride accelerated colonic luminal transit. On the other hand, cisapride and mosapride failed to enhance colonic transit. These results demonstrate that itopride has a stimulatory action on colonic peristalsis, propelling colonic luminal contents, different from that of cisapride and mosapride. Therefore, itopride may be a useful drug for the treatment of functional bowel disorders such as functional constipation.

背景与目标： ：我们研究了胃动力药伊托必利盐酸盐（异丙托必利盐酸盐，N- [4- [2-（二甲基氨基）乙氧基]苄基] -3,4-二甲氧基苯甲酰胺盐酸盐）对结肠运动活性的影响，在体内和体外，与苯甲酰胺，西沙必利水合物（西沙必利）和柠檬酸莫沙必利（莫沙必利）相比。依托必利可通过对分离的豚鼠结肠施加腔内压力来刺激蠕动和节段运动。尽管西沙必利和莫沙必利增强了节段运动能力，但它们明显降低了蠕动能力。在植入应变计力传感器的清醒犬中，伊托必利会刺激从胃到结肠的胃肠道收缩活动。西沙必利刺激胃窦，回肠和升结肠的收缩活动。莫沙必利仅在胃窦和回肠中刺激收缩活动。在豚鼠和大鼠中，伊托必利加快了结肠腔的转运。另一方面，西沙必利和莫沙必利不能促进结肠转运。这些结果表明伊托必利对结肠蠕动具有刺激作用，促进结肠腔内物质的含量，与西沙必利和莫沙必利不同。因此，伊托必利可能是用于治疗功能性肠病如功能性便秘的有用药物。