• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.419-426
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• 2019

Mosapride accelerates gastric emptying by acting on 5-hydroxytryptamine type 4 ($5-HT_4$) receptor and is frequently used in the treatment of gastrointestinal (GI) disorders requiring gastroprokinetic efficacy. We tested the effect of mosapride on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents because the $5-HT_3$ receptors are also known to be expressed in the GI system and have an important role in the regulation of GI functions. Using the whole-cell voltage clamp method, we compared the currents of the $5-HT_3$ receptors when 5-HT was applied alone or was co-applied with mosapride in cultured NCB-20 cells known to express $5-HT_3$ receptors. The $5-HT_3$ receptor current amplitudes were inhibited by mosapride in a concentration-dependent manner. Mosapride blocked the peak currents evoked by the application of 5-HT in a competitive manner because the $EC_{50}$ shifted to the right without changing the maximal effect. The rise slopes of $5-HT_3$ receptor currents were decreased by mosapride. Pre-application of mosapride before co-application, augmented the inhibitory effect of mosapride, which suggests a closed channel blocking mechanism. Mosapride also blocked the opened $5-HT_3$ receptor because it inhibited the $5-HT_3$ receptor current in the middle of the application of 5-HT. It accelerated desensitization of the $5-HT_3$ receptor but did not change the recovery process from the receptor desensitization. There were no voltage-, or use-dependency in its blocking effects. These results suggest that mosapride inhibited the $5-HT_3$ receptor through a competitive blocking mechanism probably by binding to the receptor in closed state, which could be involved in the pharmacological effects of mosapride to treat GI disorders.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.84-89
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• 2011

The present study was undertaken to determine whether combined treatment with prokinetic trimebutine and mosapride has a synergic effect on gastrointestinal motility and visceral pain associated with gastrointestinal dysfunction. To develop effective gastroprokinetic agents with greater potencies than trimebutine or mosapride for the treatment of gastrointestinal tract disease, a mixture of trimebutine and mosapride was designed and prepared. In the present study, treatment with trimebutine alone showed a dose-dependent effect on propelling movements of normal small and large intestine in mice, whereas mosapride effected only small intestine motility. Co-administration of trimebutine with mosapride, a well-established prokinetic drug, produced a synergistic influence on normal small intestine motility, but demonstrated an unclear effect on large intestine motility, with a slight tendency to reduce the propelling time. In a stress model, the small and large intestine motilities were significantly decreased. The reduction of intestine motility was restored to a normal level and the restoring effect was more pronounced in the combined treatment with trimebutine plus mosapride than treatment with trimebutine or mosapride alone. Furthermore, treatment with trimebutine plus mosapride significantly decreased acute visceral pain which was not controlled by trimebutine or mosapride alone. These data suggest that combination therapy with trimebutine plus mosapride has a synergic effect on small and large intestine motility and visceral pain control in gastrointestinal disorders.

• 대한수의학회지
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• 제52권3호
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• pp.163-167
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• 2012

Mosapride stimulated dietary motility was introduced because of the arrhythmogenic effect of cisapride. Cisapride, 5-HT receptor agonist, induces prolongation of QT interval. Additionally, this condition can raise the possibility of acute, "malignant" arrhythmias such as torsade de pointes. It is hard to find any reports about effects of mosapride on cardiac parameters in dogs. By confirming electrocardiogram (ECG) parameters, the surface extremity leads ECG that was obtained from the four-limb electrodes and which was recorded by an ECG recorder after administration of mosapride 3 mg/kg PO b.i.d, and mosapride 3 mg/kg with itraconazole 5 mg/kg PO b.i.d, respectively. QT interval was shortened on the days of 3, 5, and post-day 1 in both mosapride 3 mg/kg administrated group and mosapride with itraconazole group. Heart rate increased significantly. QTc was slightly prolonged in mosapride administration group and mosapride with itraconazole group. However, all dogs of QTc were in normal variation (150~250 msec). Besides, the dogs showed no side effects reported in human medicine during the administration with these drugs. Although mosapride can increase the heart rate, this study suggest that mosapride may be useful for the dogs with disorders of gastrointestinal motility because of no fatal arrhythmogenic effect inspite of administration with itraconazole in dogs.

• 대한한의학회지
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• 제31권1호
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• pp.1-13
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• 2010

Objective: Functional dyspepsia is a prevalent disease. It impedes subjective quality of life. The purpose of this study was to examine the equivalent effect of herb medicine treatment (DA-9701) for functional dyspepsia. Methods: In this randomized, single-blinded, placebo-controlled study, we compared a herb medicine (DA-9701) with standard treatment (mosapride) and placebo for the treatment of functional dyspepsia. 42 volunteers who satisfied the requirements were enrolled in study. Severity of dyspepsia was measured by Nepean Dyspepsia Index (NDI) and Functional Dyspepsia Quality of Life (FD-QOL) before and after treatments. Results: 1. In the DA-9701 group, total key symptoms score was significantly lower and improve rate of key symptoms was higher than in the mosapride and placebo groups, but there were no statistically significant differences between three groups. 2. In the DA-9701 and mosapride groups, "nausea" and "bad breath" were significantly lower compared with the placebo group. 3. In the DA-9701 group, NDI Quality of Life scores were significantly higher, but there were no [other] statistically significant differences between the three groups. 4. In the DA-9701 and mosapride groups, FD-QOL scores were higher compared with the placebo group, but there were no statistically significant differences between the three groups. Conclusion: Herb medicine treatment (DA-9701) is effective to improve the symptoms and quality of life in patients with functional dyspepsia.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.486-492
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• 2015

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their interassay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.

• 대한한방내과학회지
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• 제35권4호
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• pp.439-447
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• 2014

Objectives: The aim of this study was to investigate whether 1) variation of bowel sounds recorded stably through an electronic stethoscope in a sound insulation box can be related with that of gastric contraction and 2) if they are thus useful tool in the measurement of the gastric contractility in awake rats or not. Methods: Electrical potentials of both electronic stethoscope of bowel sound and force transducer were recorded simultaneously and continuously in the sound insulation box for the starting 30 min of basal state, and then 30 min of 0.2 ml normal saline administration, finally 30 min of 0.2 ml mosapride citrate solution (100 mg/Kg) in rats. Each motility index of normal saline or mosapride citrate treatment was presented with ratio against the basal state by using integrated electrical potentials. Results: A pattern of significance of gastric contractility between bowel sound and force transducer was showed analogously. Conclusions: The amplitude of bowel sounds recorded by the electronic stethoscope related with the intensity of gastric contractions. This confirms that a sound insulation box and electronic stethoscope are useful tools in the measurement of the gastric contractility of awake rats.

• 한국임상수의학회지
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• 제30권3호
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• pp.193-195
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• 2013

1년 6개월령 몸무게 7.7 kg의 수컷 Cocker Spaniel이 일주일 동안 지속된 역류성 구토를 주 증으로 진료 의뢰되었다. 기본 검사와 X선 투시진단법을 통해 식도운동성 저하로 진단하였다. 치료약물로는 mosapraide를 투여하였고, 습식 사료를 소량씩 자주 일어선 자세로 급여하는 방법을 통해 치료하였다. 3개월 후 재검사에서 임상증상의 개선과 X선 투시진단법 상 식도운동성의 개선이 있었으며, 첫 내원 시 식도 통과 시간이 18초였던 것에서 8초까지로 개선되었다. 본 케이스는 식도거대증을 동반하지 않으면서, 운동성만 저하된 질병으로 한국에서는 첫 보고이다.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.507-515
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• 2021

Postoperative ileus (POI), a symptom that occurs after abdominal surgery, reduces gastrointestinal motility. Although its mechanism is unclear, POI symptoms are known to be caused by inflammation 6 to 72 h after surgery. As proton pump inhibitors exhibit protective effect against acute inflammation, the purpose of this study was to determine the effect of ilaprazole on a POI rat model. POI was induced in rats by abdominal surgery. Rats were divided into six groups: control: normal rat + 0.5% CMC-Na, vehicle: POI rat + 0.5% CMC-Na, mosapride: POI rat + mosapride 2 mg/kg, ilaprazole 1 mg/kg: POI rat + ilaprazole 1 mg/kg, ilaprazole 3 mg/kg: POI rat + ilaprazole 3 mg/kg, and ilaprazole 10 mg/kg: POI rat + ilaprazole 10 mg/kg. Gastrointestinal motility was confirmed by measuring gastric emptying (GE) and gastrointestinal transit (GIT). In the small intestine, inflammation was confirmed by measuring TNF-α and IL-1β; oxidative stress was confirmed by SOD, GSH, and MDA levels; and histological changes were observed by H&E staining. Based on the findings, GE and GIT were decreased in the vehicle group and improved in the ilaprazole 10 mg/kg group. In the ilaprazole 10 mg/kg group, TNF-α and IL-1β levels were decreased, SOD and GSH levels were increased, and MDA levels were decreased. Histological damage was also reduced in the ilaprazole-treated groups. These findings suggest that ilaprazole prevents the decrease in gastrointestinal motility, a major symptom of postoperative ileus, and reduces inflammation and oxidative stress.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.267-272
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• 2011

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the $5HT_2$ receptor antagonist ketanserin and the $5-HT_3$ receptor antagonist ondansetron but was inhibited by the 5-$HT_1$ receptor antagonist methysergide and 5-$HT_4$ receptor antagonist GR113808. These results indicate that 5-$HT_1$ and 5-$HT_4$ receptors may mediate the contraction of the 5-HT-induced response and 5-$HT_2$ and 5-$HT_3$ receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

• 한국식품영양과학회지
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• 제42권12호
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• pp.2076-2081
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• 2013

본 연구는 cisplatin 및 atropine으로 유발된 기능성소화불량증 동물모델에서 MMSC의 위 배출능 및 위장관 전이 지연의 개선 효과를 연구한 후, 기능성소화불량증을 치료하기 위한 약물의 기초자료를 제공하고자 하였다. 기능성소화불량은 뚜렷한 기질적 병변 없이 여러 가지 다양한 소화불량 증상에 의한 진단이기 때문에 치료 또한 단순하지가 않다. 대부분의 증상이 호전과 악화를 반복하며 음식, 스트레스 등에 의해 변화가 심하므로 임상적으로 효과 판정이 어렵고, 더욱이 위약만을 투여하더라도 증상의 호전이 있을 수 있으므로 어떠한 치료가 의미 있게 효과가 있는지를 판단하는데 애로점이 많다. 이번 연구에 대조물질로 비교한 약물도 현재 사용되는 위장질환 치료물질로 위 배출능에서 시험물질보다 좋은 결과 값을 얻었지만, 위장관 전이 지연 개선 실험에서 시험물질 MMSC와 비교하였을 때 약물의 효과가 다르게 나타났다. 결론적으로 MMSC를 투여한 그룹이 유발그룹에 비해 위 배출능 및 위장관의 전이 비율이 유의적으로 증가하였음을 확인하였다. 위장관 운동 촉진제로 시판되는 약물을 투여한 그룹보다는 그 비율이 다소 낮게 관찰되었지만 시판 약물의 고용량 투여와 비교하여 저용량의 MMSC에도 불구하고 위배출능의 효과를 확인하였으므로 고용량의 MMSC투여 시 위 배출능의 개선 효과가 높게 관찰될 가능성 역시 배제할 수 없어 향후 보다 구체적인 연구가 수행되어야 할 것으로 판단된다.