• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권sup1호
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• pp.30-37
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• 2008

The knowledge of motility disorders of the gastrointestinal tract has increased over the past decades. The development of newer therapies for bowel motility disorders has been disappointingly slow. Prokinetic agents are medications that enhance coordinated gastrointestinal motility and transit of material in the gastrointestinal tract. These agents are pharmacologically and chemically diverse. However, life-threatening adverse effects of prokinetic agents such as cisapride was present. In this review, pharmacologic effects and use of prokinetic agents in children was introduced.

• 대한기관식도과학회지
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• 제4권2호
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• pp.193-196
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• 1998

Gastroesophageal reflux (GER) has been considered one of major causes in patient with globus symptom. Diagnostic methods for GER are gastroesophagoscopy, acid perfusion test esophagogram, esophageal manometry, 24-hour double probe pH-metry, and so on. According to the literature, positive rate of GER on esophagogram was reported variably from 4.7% to 45.9% and the outcome of classical treatment with antacid and prokinetic agent was reported from 70% to 84%. We reviewed the medical records of 81 patients with globus symptom. Each patient had been performed esophagogram and treated with antacid and prokinetic agent. Positive rate of GER on esophagogram was 46.9%. Complete resolution and improvement of globus symptom was 79% overally, 92% in positive group of GER rut esophgogram, and 72% in negative group. Considering aspects of time-cost and compliance of patient esophagogram is one of the screening methods of GER in patients with globus symptom. Antacid and prokinetic agent is recommended in treatment of patients with globus symptom.

• 동의생리병리학회지
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• 제21권6호
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• pp.1549-1554
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• 2007

To verify the effects of JAUN-1, which is a water-extracted herbal mixture, on gastroenteric disorders induced by 0.1 percent of iodoacetamide (IA) in rats. We divided four groups, $Na{\"{\i}}ve$ + Distilled Water (DW), 0.1% IA + DW, 0.1% IA + Proton pump inhibitor (Lansoprazole, 5 mg/kg) and 0.1% IA + Herbal mixture (JAUN-1, 50mg/kg) and performed following experimental methods to confirm its advantageous effects against ulcerogenic stomach in rats induced by 0.1% IA; cell cytotoxicity, analysis of lesions score, Hematoxylin & Eosin (H&E) stain, RT-PCR for ${\beta}-actin$, COX-1 and COX-2 and evaluation of intestinal prokinetic activity. No cytotoxicity was elucidated at the concentration of 1, 5, 10, 50, 100, $500\;{\mu}g/ml$ and 1mg/ml JAUN-1 through MTT Assay using by human stomach epithelial AGS cells, respectively. In addition, the JAUN-1 treated group and the lansoprazole treated group significantly decreased in lesions score compared to the DW treated group in the gastritis induced rat model, and results of immunohistochemistry by H&E staining showed that histological recovery in Proton Pump Inhibitor (PPI) and JAUN-1 treated groups rather than the DW administrated group. Another outcome was that ${\beta}-actin$ relative COX-2 expression level was significantly promoted in the DW treated group while ${\beta}-actin$ relative COX-1 expression level was no meaningful change in this rat model. Finally, intestinal prokinetic activity was recovered from low level of prokinetic activity due to 0.1% IA induced gastritis to the similar level of Normal group. These results suggested that JAUN-1 may have beneficial effects against 0.1% IA-induced gastritis rat model through decreasing lesions score, histological recovery, ${\beta}-actin$ relative COX-1, 2 expression level and prokinetic activity.

• 생명과학회지
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• 제29권6호
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• pp.735-739
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• 2019

용담(Gentiana scabra)의 근경 및 뿌리를 말린 한약재는 우리나라, 중국, 일본을 포함하는 동아시아 지역에서 아주 오래 전부터 각종 염증성 피부 질환, 소화불량, 식욕부진, 위염, 당뇨병 등의 치료를 목적으로 한의학에서 널리 처방되어 왔다. 본 연구에서는 용담이 위장관 운동 기능에 미치는 영향을 검정하기 위해 용담의 열수 및 에탄올 추출물을 각각 제조하였으며, 마우스에서 in vivo 위 배출 속도 및 위장관 이송률을 측정하는 실험을 수행하였다. 위 배출 속도는 용담 열수 추출물 1 g/kg 투여 시 유의적으로 증가하였다. 위장관 이송률은 용담 열수 추출물 0.1 및 1 g/kg 투여 시, 그리고 용담 에탄올 추출물 1 g/kg 투여 시 유의적으로 증가하였으며, 두 추출물 모두 용량 의존적 증가 양상을 보였다. 더욱이, 용담 열수 추출물 1 g/kg 투여 시의 위장관 이송률은, 1990년대까지 임상에서 가장 강력한 위장관 운동 촉진제로 쓰였으나 2000년 이후 부작용으로 시장에서 철수된 약물인 cisapride 투여 시보다 그 수치가 높았다. 이러한 결과들은 용담 열수 추출물이 잠재적으로 cisapride를 대체할 수 있는 위장관 운동 촉진제로 개발 가능한 후보 물질임을 시사한다.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.110.1-110.1
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• 2001

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
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• pp.267.1-267.1
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• 2000

• 생명과학회지
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• 제24권3호
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• pp.260-265
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• 2014

귤나무(Citrus unshiu)의 과피를 말린 한약재인 진피(Aurantii Nobilis Pericarpium; ANP)는 오래 전부터 대한민국을 비롯한 동아시아에서 위장관 운동 관련 질환의 치료에 전통적으로 쓰여 왔다. 본 연구에서는 진피 주정 추출물(ANP-E)을 제조하여 실험하였는데, 우선 ANP-E는 5 g/kg의 고용량을 mouse에 경구 투여하였을 때에도 급성독성을 나타내지 않았다. ANP-E가 위장관 운동 기능에 미치는 영향을 파악하고 이를 cisapride의 효과와 비교하기 위하여, mouse를 대상으로 위장관 이송률을 측정하는 실험을 수행하였다. Cisapride는 20세기 말까지 다양한 위장관 운동 저해 상황에서 임상적으로 광범위하게 적용되었던 최고의 위장관 운동 촉진제였으나, 치명적인 부작용으로 인하여 2000년 이후 시장에서 철수된 약물이다. 실험 결과, ANP-E는 정상 및 위장관 운동 저해 상황에서 모두 용량 의존적으로 위장관 운동을 촉진시키는 것으로 나타났다. ANP-E의 위장관 운동 촉진 효과를 cisapride와 비교해 보면, 정상 mouse에서는 cisapride와 거의 대등한 위장관 이송률 수치를 나타내었으며, 특히 위장관 운동 저해 상황에서는 cisapride보다 약효 및 안전성 측면에서 모두 비교 우위를 점하는 강력한 위장관 운동 기능개선 효과를 보였다. 이상과 같은 결과들은, ANP-E가 인간의 위장관 운동 기능 저해 상황을 개선할 수 있는 새롭고 강력한 신약 후보 물질이자, 아직 시장에 출현하지 않고 있는 cisapride의 대체 의약품으로서 개발 가능함을 시사하고 있다.

• 동의생리병리학회지
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• 제22권6호
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• pp.1518-1524
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• 2008

Ponciri Fructus (PF), the immature fruit of Poncirus trifoliata, has been used for treatment of constipation in Korean traditional medicine. It has been reported that PF has a prokinetic effect on gastrointestinal tract, but little is known about the effect on colonic contraction. The aim of this study was to investigate the effect of PF on spontaneous contractions of proximal and distal colon in rats. The aqueous extract of PF was centrifuged and filtered and its supernatant was used for in vitro motility study. The removed colon from rats was divided into proximal and distal segments. Each segment was mounted in a 10 ml organ bath and measured the change of the spontaneous contraction with increasing dose (1, 5, 10, 50, 100, 500, $1000{\mu}g/ml$) of PF extract administration. Also the effect of PF on the spontaneous contraction was measured under treatment of atropine, acetylcholine (Ach), and tetrodotoxin (TTX). PF increased the spontaneous phasic contraction of distal colon dose dependently, but there was no change in proximal colon. The contractile response induced by PF in distal colon was lower than that of Ach and was partially blocked by atropine ($10^{-6}M$). TTX increased the spontaneous contraction and it was reinforced with Ach addition. But the extract of PF had no or little contractile effect of TTX in colon. PF increased spontaneous contractions selectively in distal colon. The prokinetic effect of PF may be due to enhancement of cholinergic related excitatory neural system.

• 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.

• Molecules and Cells
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• 제27권3호
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• pp.307-312
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• 2009

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by $GDP-{\beta}-S$, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external $Ca^{2+}$ influx, phospholipase C activation, and $Ca^{2+}$ release from internal storage in a G protein-independent and protein kinase C-independent manner.