motilin and Gastroparesis

Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms.. Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another?. Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use.. Vomiting: Rationale for 5-HT. Several drug classes inhibiting vomiting have no scientific rationale. NK

Topics: Gastric Emptying; Gastroparesis; Humans; Motilin; Nausea; Serotonin; Vomiting

The prevalence of gastroparesis is increasing. Diabetes mellitus and sequelae of œsogastric surgery are the two main causes of gastroparesis. In some patients, gastroparesis seems a postinfectious disease after its sudden onset after a viral infection. In about one third of the patients, gastroparesis is considered as idiopathic. In diabetic patients, gastroparesis impairs glycaemic control. Due to the low positive predictive value of symptoms, a gastric emptying study is often necessary to confirm a suspected diagnosis of gastroparesis. The symptomatic efficacy of erythromycin is higher than that of other prokinetics. This efficacy is higher when erythromycin is given intravenously. Hyperglycaemia impairs this symptomatic effect. Due to a tachyphylaxis phenomenon, the clinical effect of erythromycin decreases with the duration of treatment. In refractory gastroperis, either duodenal or jejunal enteral feeding, or high-frequency gastric electrical stimulation are possible therapeutic options while endoscopic alternatives (intrapyloric botulinum injection or pyloric balloon dilation) give unsatisfactory results.

Topics: Digestive System Surgical Procedures; Electric Stimulation Therapy; Erythromycin; Gastroparesis; Humans; Motilin; Treatment Failure

Gastroparesis is a symptomatic chronic disorder characterized by delayed gastric emptying without a mechanical obstruction. Gastroparesis is most often associated with diabetes, gastric surgery, and systemic disorders affecting the neuromuscular control of the stomach. However, no underlying etiology can be found in up to 40% of patients, a condition referred to as idiopathic gastroparesis. Due to the numerous potential etiologies and the highly variable clinical manifestations, the management of gastroparesis is particularly challenging. The purpose of this review is to provide an update on the use of antiemetics, prokinetics, and tricyclics for the treatment for nausea and vomiting associated with gastroparesis.

Topics: Antidepressive Agents, Tricyclic; Antiemetics; Dopamine Antagonists; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Motilin; Nausea; Vomiting

A 75-year-old woman who had undergone a hysterectomy with adnexectomy followed by radiotherapy for endometrial carcinoma complained of postprandial nausea with vomiting after eating solid foods and of cramp-like abdominal pain, but her appetite was good. She had lost 25 kg in weight over 13 months.. Physical examination, laboratory tests, radiology and gastroscopy were unremarkable. Gastric scintigraphy showed abnormally prolonged emptying.. Nausea and vomiting stopped at once after erythromycin (a motilin agonist) had been administered. It was at first given intravenously after meals (50 mg three times daily for 5 days), then orally for 10 weeks (250 mg three times daily before meals). Subsequent examination revealed normal gastric emptying. The symptoms did not recur after erythromycin had been discontinued.. Erythromycin is an effective drug against gastroparesis caused by radiotherapy, because it acts even when the enteric nerves are damaged.

Topics: Aged; Endometrial Neoplasms; Erythromycin; Female; Gastric Emptying; Gastroparesis; Humans; Motilin; Radiotherapy, Adjuvant

The study aimed to investigate the associations between glycaemic control after acute pancreatitis and gastrointestinal motility, using plasma motilin concentration and gastroparesis cardinal symptom index score as proxies.. This cross-sectional study recruited a total of 93 individuals after acute pancreatitis. Gastroparesis cardinal index scores, demographic and anthropometric factors, as well as pancreatitis-related factors were analysed. Fasting venous blood was collected to measure motilin, glycated haemoglobin, and fasting blood glucose. Linear regression analyses were conducted to investigate the associations between glycaemic control and gastrointestinal motility in unadjusted and adjusted models.. Motilin was significantly higher in individuals with diabetes across all adjusted models, with the highest ß-coefficient (95% confidence interval) of 588.89 (138.50, 1039.28); P=0.010. Fasting blood glucose was significantly associated with motilin across all models, with the highest ß-coefficient (95% confidence interval) of 156.30 (55.49, 257.10); P=0.002. Glycated haemoglobin was significantly associated with motilin in one adjusted model with ß-coefficient (95% confidence interval) of 18.78 (1.53, 36.02); P=0.033. Gastroparesis cardinal symptom index was not significantly associated with any measure of glycaemic control.. Diabetes in individuals after acute pancreatitis appears to be characterised by elevated plasma motilin but not gastroparesis cardinal symptom index. The role of motilin in this setting warrants further investigations.

Topics: Adult; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus; Female; Gastroparesis; Humans; Male; Middle Aged; Motilin; Pancreatitis

To observe the curative effect of autologous blood point injection on diabetic gastroparesis and to study its underlying mechanism.. A total of 42 type-II diabetes outpatients and inpatients were randomly and equally divided into treatment group and control group according to a random digit table. Patients of the treatment group were treated by injection of the patient's own venous blood (2 mL/acupoint) into the unilateral Zusanli (ST 36), Zhongwan (OV 12) and Weishu (BL 21), once every week, 4 times together. Patients of the control group were ordered to take motilium (10 mg/time), 3 times daily for 4 weeks. Plasma motilin and gastrin were detected by radioimmunoassay before and 4 weeks after the treatment.. Of the two 21 cases in the control and treatment groups, 3 and 7 experienced marked improvement in their symptoms, 4 and 8 were effective, 14 and 6 were failed in the treatment, with the effective rates being 33.3% and 71.4% respectively. The effective rate of the treatment group was significantly higher than that of the control group (P<0.05). The contents of plasma motilin and gastrin in both control and treatment groups were reduced obviously after the treatment (P<0.01), and the effect of the treatment group was significantly superior to that of the control group in lowering plasma motilin and gastrin levels (P<0.01).. Acupoint injection of the diabetes patients' own blood can obviously alleviate the symptoms of diabetic gastroparesis, which is closely associated with its effects in lowering plasma motilin and gastrin levels.

Topics: Acupuncture Points; Adolescent; Adult; Aged; Blood Transfusion, Autologous; Diabetes Complications; Female; Gastrins; Gastroparesis; Humans; Injections; Male; Middle Aged; Motilin; Treatment Outcome; Young Adult

The current pharmacological management of diabetic gastroparesis remains difficult. Acupuncture has been widely used for gastrointestinal symptoms. The aim of this study was to investigate the effects of electroacupuncture (EA) on solid gastric emptying time, serum gastrin, motilin, pancreatic polypeptide (PP), fasting and postprandial blood glucose, and symptoms in patients with diabetic gastroparesis.. EA at the Zusanli (ST 36) and Hegu (LI 4) points and sham EA as control were administered by an experienced and licensed acupuncturist.. This was a pilot study with a randomized, single-blinded design.. Nineteen (19) patients with type 2 diabetes who had had symptoms of gastroparesis for more than 3 months were included in the trial and randomized into two groups. Each group received EA (n = 9) or sham EA (n = 10) consisting of 4 sessions over 2 weeks.. Symptom severity was evaluated using the Gastroparesis Cardinal Symptom Index (GCSI) at baseline, at the end of treatment, and 2 weeks after the end of the trial; solid-phase gastric half-emptying time was measured by scintigraphy; in addition, serum gastrin, motilin, PP, fasting, and postprandial blood glucose levels were also measured.. Gastric half-emptying time in 9 patients with diabetic gastroparesis was significantly shortened by EA treatment (143.8 +/- 55.9 minutes versus 98.8 +/- 28.6 minutes, p < 0.03). Half-emptying time did not change (98.9 +/- 26.4 minutes versus 90.9 +/- 24.8 minutes, p > 0.05) in the sham EA group. Symptom severity, as measured by GCSI total score, improved significantly both at the end of treatment (2.38 +/- 0.56 versus 1.48 +/- 0.19, p < 0.001) and 2 weeks after the end of the trial (2.38 +/- 0.56 versus 1.65 +/- 0.44, p < 0.01) when compared with the baseline in the EA group, but did not change from baseline with sham EA treatment. There were no significant changes in fasting and postprandial blood glucose, serum gastrin, motilin, and PP in both groups. No significant adverse events occurred.. This study demonstrates that short-term EA at the Zusanli and Hegu points effectively reduces the dyspeptic symptoms of diabetic gastroparesis and accelerates solid gastric emptying. Sustained improvement in dyspeptic symptoms was observed at 2 weeks after the end of the trial. Its potential for treating gastroparesis may be explored, and a larger trial is required to draw definitive conclusions.

Topics: Adult; Diabetes Complications; Electroacupuncture; Female; Gastric Emptying; Gastrins; Gastroparesis; Humans; Male; Middle Aged; Motilin; Pilot Projects; Postprandial Period; Severity of Illness Index; Single-Blind Method; Treatment Outcome

Mitemcinal, an oral motilin agonist, accelerates gastric emptying.. To investigate if mitemcinal was superior to placebo in relief of symptoms attributed to gastroparesis.. In a randomized, double-blind design, 392 insulin-requiring diabetics with symptoms attributable to gastroparesis were treated for 3 months with placebo, mitemcinal 5 or 10 mg bid. On a weekly basis, patients assessed whether there was adequate relief of their gastroparesis symptoms. Patients were classified as Complete Responders (CR) if there were three consecutive positive monthly responses, which required at least 50% of their weekly responses in a month being positive. An Overall Responder (OR) had at least 75% positive weekly responses for the whole treatment period.. Mitemcinal 10 mg produced a significantly better response rate than placebo with a 10.6% increase in the OR (P < 0.05 vs. placebo). Mitemcinal 10 mg also produced statistically significant increases in the CR and OR in the subgroup identified by baseline body mass index (<35 kg/m(2)) and haemoglobin A(1c) (<10%) (P < 0.01 vs. placebo). Adverse events did not differ from placebo frequency levels.. Mitemcinal can induce a statistically significant response to treatment in a subset of diabetic gastroparesis where future prokinetic clinical trials should be focused.

Topics: Adolescent; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastrointestinal Agents; Gastroparesis; Humans; Male; Motilin; Safety; Treatment Outcome

Mitemcinal is an orally active motilin agonist that could potentially improve gastric emptying.. To investigate the effect of mitemcinal on gastric emptying in patients with idiopathic and diabetic gastroparesis.. In a randomized, double-blind design, 106 patients were randomized into four dosing regimens (22 to placebo and 21 each to mitemcinal 10 mg, 20 mg, 30 mg bid or 20 mg tid) for 28 days. A standardized scintigraphic gastric emptying test was performed at screening and again after completing the 4-week protocol.. All doses of mitemcinal showed prokinetic activity. A significant improvement in meal retention at 240 min was noted even in the lowest dose group with the greatest improvement observed with 30 mg bid group (75% vs. 10% in placebo group). Diabetic patients responded better than the idiopathic subgroup. In diabetic patients, blood glucose at 1 h after a meal showed dose-dependent elevation. Although gastroparetic symptoms improved with both mitemcinal and placebo, the prominent placebo effect was not statistically exceeded by mitemcinal. Baseline scintigraphy results exhibited no clear correlation between the severity of gastroparetic symptoms and the status of gastric emptying.. Mitemcinal is capable of accelerating gastric emptying in both diabetic and idiopathic patients with gastroparesis.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Erythromycin; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Male; Middle Aged; Motilin; Placebos; Treatment Outcome

KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans.. To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis.. Twenty-nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and 'meal-related' symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days.. KC 11458 had no statistically significant or clinically relevant effect on gastric emptying of either the solid intragastric retention at 100 min (T100) (P = 0.87) or liquid 50% emptying time (T50) (P = 0.17) components of the meal. KC 11458 slightly worsened (P = 0.04) upper gastrointestinal symptoms when compared with placebo. The magnitude of the change in solid gastric emptying correlated with the change in the blood glucose concentration (r = 0.49; P < 0.05).. KC 11458, in a dose of 8 mg t.d.s. for 8 days, does not accelerate gastric emptying in patients with diabetic gastroparesis. The absence of efficacy may relate to an effect of hyperglycaemia.

Topics: Autonomic Nervous System Diseases; Blood Glucose; Diabetes Mellitus; Diabetic Neuropathies; Erythromycin; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Motilin

Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with and without delayed gastric emptying.. Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C(13) octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Patients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual analogue scales; the primary outcome was assessment of change in the total upper abdominal symptom severity score (range 0-800 mm) from baseline to the final visit.. The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvement on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to treat). The results were not significantly different in those with and without delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dependently in a greater number of patients receiving ABT-229 than placebo. Overall, 63% of patients on placebo reported a good or excellent global response, and this was not different from the active treatment arms.. The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Breath Tests; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Erythromycin; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Male; Middle Aged; Motilin; Regression Analysis; Treatment Outcome

Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction.. Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months were enrolled. Two acupuncture needles were inserted into the subjects' legs at the Zusanli points, and electrical stimulation (2-Hz pulses) was delivered for 30 min. Cutaneous electrogastrography was performed for 30 min at baseline, for 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide levels were also measured.. There was a significant increase in the percentages of normal frequency during and after acupuncture (baseline vs. acupuncture and after acupuncture 21.99 +/- 19.38% vs. 45.93 +/- 19.72 and 48.92 +/- 19.56%; p < 0.01). In addition, the percentage of tachygastric frequency was decreased significantly during and after acupuncture. The dominant frequency was also changed significantly. There was an increase of serum human pancreatic polypeptide during acupuncture (baseline vs. acupuncture 56.96 +/- 27.64 vs. 73.11 +/- 22.37 pmol/l; p < 0.05).. The results of this study revealed that electrical stimulation at the Zusanli points could increase the percentage of normal electrogastrography frequency and decrease the percentage of tachygastric frequency in diabetic patients. The data indicate that acupuncture may enhance the regularity of gastric myoelectrical activity in diabetic patients.

Topics: Acupuncture Points; Adult; Aged; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Electroacupuncture; Female; Gastrins; Gastrointestinal Motility; Gastroparesis; Humans; Male; Middle Aged; Motilin; Pancreatic Polypeptide; Pilot Projects

Motilin is a 22-amino-acid gastrointestinal (GI) hormone and is involved in the regulation of GI motility through binding to GPR38, the motilin receptor which is expressed on smooth muscle cells in the GI tract. Therefore, GPR38 agonists are expected to be novel gastrointestinal prokinetic agents for the treatment of functional gastrointestinal disorders such as gastroparesis and chronic constipation. We identified a series of N-methylanilide derivatives as novel non-macrolide GPR38 agonists. Among them, 12 di-l-tartrate (DS-3801b) was selected as a clinical candidate for further evaluation.

Topics: Aniline Compounds; Animals; Cyclohexanes; Dose-Response Relationship, Drug; Drug Discovery; Gastrointestinal Agents; Gastroparesis; Humans; Molecular Structure; Piperazines; Rabbits; Receptors, G-Protein-Coupled; Structure-Activity Relationship

To investigate the effects of gastric pacing on gastric emptying and plasma motilin level in a canine model of gastric motility disorders and the correlation between gastric emptying and plasma motilin level.. Ten healthy Mongrel dogs were divided into: experimental group of six dogs and control group of four dogs. A model of gastric motility disorders was established in the experimental group undergone truncal vagotomy combined with injection of glucagon. Gastric half-emptying time (GEt(1/2)) was monitored with single photon emission computerized tomography (SPECT), and the half-solid test meal was labeled with an isotope-(99m)Tc sulfur colloid. Plasma motilin concentration was measured with radioimmunoassay (RIA) kit. Surface gastric pacing at 1.1-1.2 times the intrinsic slow-wave frequency and a superimposed series of high frequency pulses (10-30 Hz) was performed for 45 min daily for a month in conscious dogs.. After surgery, GEt(1/2) in dogs undergone truncal vagotomy was increased significantly from 56.35+/-2.99 min to 79.42+/-1.91 min (P<0.001), but surface gastric pacing markedly accelerated gastric emptying and significantly decreased GEt(1/2) to 64.94+/-1.75 min (P<0.001) in animals undergone vagotomy. There was a significant increase of plasma level of motilin at the phase of IMCIII (interdigestive myoelectrical complex, IMCIII) in the dogs undergone bilateral truncal vagotomy (baseline vs vagotomy, 184.29+/-9.81 pg/ml vs 242.09+/-17.22 pg/ml; P<0.01). But plasma motilin concentration (212.55+/-11.20 pg/ml; P<0.02) was decreased significantly after a long-term treatment with gastric pacing. Before gastric pacing, GEt(1/2) and plasma motilin concentration of the dogs undergone vagotomy showed a positive correlation (r=0.867, P<0.01), but after a long-term gastric pacing, GEt(1/2) and motilin level showed a negative correlation (r=-0.733, P<0.04).. Surface gastric pacing with optimal pacing parameters can improve gastric emptying parameters and significantly accelerate gastric emptying and can resume or alter motor function in a canine model of motility disorders. Gastric emptying is correlated well with plasma motilin level before and after pacing, which suggests that motilin can modulate the mechanism of gastric pacing by altering gastric motility.

Topics: Animals; Dogs; Electric Stimulation Therapy; Female; Gastric Emptying; Gastroparesis; Male; Motilin

The gastroprokinetic effects of de(N-methyl)-N-isopropyl-8, 9-anhydroerythromycin A 6,9-hemiacetal (EM574), a non-peptide motilin receptor agonist, were investigated in conscious dogs in a normal state and with experimentally-induced gastroparesis. Gastric emptying of semi-solid meals was assessed indirectly from acetaminophen absorption with simultaneous recording of gastric antral motility. In the normal state, post-prandial intraduodenal administration of EM574 (0.03 mg/kg) [corrected] stimulated antral motility and significantly enhanced gastric emptying as potently as did intravenous porcine motilin (0.003 mg/kg/h). Intraduodenal cisapride at 1 mg/kg denal cisapride at 1 mg/kg elicited antral contractions and tended to accelerate gastric emptying but at 3 mg/kg, gastric emptying was not enhanced despite a further increase in the motor index. In dogs with gastroparesis induced by intraduodenal oleic acid or intravenous dopamine, EM574 (0.03 mg/kg) increased antral motility and reversed the delayed gastric emptying completely. Cisapride (1 mg/kg) partially ameliorated the impaired emptying under these conditions. In atropinized dogs, no acceleration of gastric emptying by EM574 was observed. These results indicate that EM574 potently accelerates gastric emptying of caloric meals in dogs in a normal state and with experimentally-induced gastroparesis, and also suggest that the effect is mediated through stimulation of a cholinergic neural pathway.

Topics: Animals; Atropine; Cisapride; Dogs; Erythromycin; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Male; Motilin; Muscarinic Antagonists; Receptors, Serotonin; Receptors, Serotonin, 5-HT4; Serotonin Receptor Agonists

Early gastric stasis is a unique complication of pylorus-preserving pancreatoduodenectomy. Because the duodenum proved to be important in the initiation and consolidation of phase III activity of the migrating motor complex of the stomach, the absence of the duodenum and hence gastric phase III may be a cause of gastric stasis.. Postoperative gastrointestinal motility was measured with a pneumohydraulic capillary infusion system in nine patients who had undergone pylorus-preserving pancreatoduodenectomy through an indwelling tube assembly placed at operation, and compared with that in six patients who had undergone duodenum-preserving pancreatic head resection. Plasma motilin concentrations were measured by radioimmunoassay.. The mean period until the first occurrence of gastric phase III was significantly longer in patients who had undergone a pylorus-preserving pancreatoduodenectomy (40.6 +/- 4.6 days or more) than in patients who had undergone a duodenum-preserving pancreatic head resection (18.8 +/- 4.3 days; p < 0.05). On the day of the first observation of gastric phase III, the plasma concentration of motilin at proximal jejunal phase III in patients who underwent a pylorus-preserving pancreatoduodenectomy (50.2 +/- 9.8 pg/ml) was significantly lower than that at duodenal phase III in patients who underwent a duodenum-preserving pancreatic head resection (184.6 +/- 48.6 pg/ml; p < 0.05).. Gastric stasis after a pylorus-preserving pancreatoduodenectomy may be in part attributable to the low concentration of plasma motilin caused by the resection of the duodenum.

Topics: Aged; Female; Gastrointestinal Motility; Gastroparesis; Humans; Male; Middle Aged; Motilin; Pancreaticoduodenectomy; Postoperative Complications; Pylorus; Time Factors