benzofurans and Gastroparesis

Gastroparesis, defined by delayed gastric emptying in the absence of mechanical outlet obstruction, is a frequent neuropathic complication of diabetes mellitus, and effective treatments are lacking. Prucalopride is a pan-gut prokinetic with selective agonist effects on serotonin 5-HT4 receptors in the gut. This study aimed to assess the effect of prucalopride 4 mg daily on Gastroparesis Cardinal Symptom Index (GCSI), meal-related symptom score (MRSS), and gastric emptying rate in diabetic or connective tissue disease (CTD)-related gastroparesis patients.. This was a double-blind crossover trial of four-week treatment periods with prucalopride or placebo divided by two weeks of washout. GSCI, MRSS, gastric emptying scintigraphy, PAGI-SYM, and PAGI-QoL were assessed at baseline and the end of each treatment period. Daily bowel movement (BM) frequency and gastrointestinal symptoms were recorded in each period.. Fifteen gastroparesis patients (13 diabetic, 2 CTD) were enrolled. GCSI scores were lower than baseline but not different between treatment arms. MRSS scores over time or cumulative score were not significantly different between groups. Gastric emptying was more rapid in the prucalopride treatment period, with mean four-hour meal retention of 22 ± 6% in PRU period vs 40 ± 9% in the placebo period (P = 0.05). Weekly BM frequency was significantly higher in prucalopride than placebo periods (10.5 ± 1.8 vs 7.5 ± 0.8, P < 0.0001). Perception of weight loss was higher in patients on prucalopride. Analysis of diabetic gastroparesis (n = 13) population did not change the conclusions.. Prucalopride at 4 mg accelerates gastric emptying and bowel movement frequency but does not appear to ameliorate gastroparesis or meal-related symptoms in this study.

Topics: Adult; Benzofurans; Cross-Over Studies; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Mitral Valve Prolapse; Myopia; Pilot Projects; Quality of Life; Radionuclide Imaging; Scleroderma, Systemic; Serotonin 5-HT4 Receptor Agonists; Skin Diseases; Treatment Outcome

Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is scarce. Prucalopride, a selective 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. In a double-blind, randomized, placebo-controlled crossover study, we evaluated the efficacy of prucalopride to improve the gastric emptying rate and symptoms in patients with gastroparesis.. Thirty-four patients with gastroparesis (28 idiopathic, 7 men, mean age 42 ± 13 years) were evaluated in a double-blind crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks of washout. The primary end point was the change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life, and daily diaries, and the gastric emptying rate was assessed by the C-octanoic acid breath test.. Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 3 patients dropped out because of adverse events of nausea and headache (all prucalopride). For the entire patient group, compared with placebo, prucalopride significantly improved the total Gastroparesis Cardinal Symptom Index (1.65 ± 0.19 vs 2.28 ± 0.20, P < 0.0001) and the subscales of fullness/satiety, nausea/vomiting, and bloating/distention. Prucalopride significantly improved the overall Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (1.15 ± 0.16 vs 1.44 ± 0.16, P < 0.05) and the domains of clothing and diet. The gastric half emptying time was significantly enhanced by prucalopride compared with placebo and baseline (98 ± 10 vs 143 ± 11 and 126 ± 13 minutes, P = 0.005 and <0.001, respectively). These significant improvements were also found when considering only the idiopathic gastroparesis subgroup.. In a cohort of patients with predominantly idiopathic gastroparesis, 4 weeks of prucalopride treatment significantly improved symptoms and quality of life and enhanced gastric emptying compared with placebo.

Topics: Adult; Benzofurans; Breath Tests; Cross-Over Studies; Double-Blind Method; Female; Gastric Emptying; Gastroparesis; Humans; Male; Quality of Life; Serotonin 5-HT4 Receptor Agonists; Severity of Illness Index

Gastroparesis is a chronic gastric disorder characterized by delayed gastric emptying without mechanical obstruction, and clinical symptoms as postprandial fullness, early satiety, bloating, nausea, vomiting, and abdominal pain. Prokinetic agents are used for the treatment of gastroparesis. Revexepride, a 5-hydroxytryptamine (serotonin) receptor (5-HT4 R) agonist, could be a good candidate drug for the gastroparesis treatment.. In the current phase II, exploratory, double-blind, randomized, stratified, placebo-controlled, repeated dose trial (EudraCT number 2007-004997-23), the efficacy on gastrointestinal symptoms and gastric emptying rate, safety, and pharmacokinetic profile of three oral doses of revexepride (0.02, 0.1, and 0.5 mg administered orally t.i.d. for 4 weeks) was evaluated in trial participants (diabetic and non-diabetic) with upper gastrointestinal tract symptoms suggestive for gastroparesis.. Eighty participants, enrolled in four parallel treatment groups, were asked to score their symptom diary data, gastroparesis cardinal symptom index (GCSI), patient assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM), quality of life questionnaires, and meal-related symptom score. Gastric emptying rate was evaluated by (13) C-octanoic acid breath test.. The severity of the symptoms assessed by means of GCSI and PAGI-SYM decreased at Week 2 and decreased further at Week 4 in all treatment groups including placebo, with similar trends in all treatment groups. Quality of life improved in all treatment groups after 4 weeks of treatment. No differences on gastric emptying rate were shown between any of the active treatment groups and placebo. Revexepride was generally safe and well-tolerated.. Four weeks of revexepride treatment did not improve symptoms or gastric emptying over placebo in patients with symptoms suggestive of gastroparesis.

Topics: Benzofurans; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Pilot Projects; Quality of Life; Serotonin 5-HT4 Receptor Agonists; Surveys and Questionnaires

Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/ kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.. La prucaloprida acelera el vaciamiento gástrico en adultos con gastroparesia. No existen estudios con este medicamento en niños con gastroparesia. Se presenta un niño de 8 años que consultó por síntomas posprandiales de un mes de duración, con diagnóstico de gastroparesia por gammagrafía de vaciamiento gástrico. No mejoró con metoclopramida, domperidona, eritromicina y esomeprazol. Recibió prucaloprida durante dos períodos (durante 178 y 376 días) a dosis de 0,03-0,04 mg/kg/ día. Presentó mejoría en el seguimiento con el índice cardinal de síntomas de gastroparesia y gammagrafías de vaciamiento gástrico. Por la buena respuesta, la prucaloprida podría ser una opción terapéutica en la gastroparesia pediátrica.

Topics: Adult; Benzofurans; Child; Domperidone; Gastric Emptying; Gastroparesis; Humans; Male

Topics: Benzofurans; Constipation; Cross-Over Studies; Gastroparesis; Humans

Topics: Benzofurans; Cross-Over Studies; Gastric Emptying; Gastroparesis; Humans

Topics: Aged; Atrial Fibrillation; Benzofurans; Catheter Ablation; Cryosurgery; Female; Gastroparesis; Humans; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Severity of Illness Index; Tomography, X-Ray Computed

We examined whether delayed gastric emptying could be produced by diabetes in dogs. Diabetes was produced by a single injection of streptozotocin (30 mg/kg i.v.), and diabetic hyperglycemia was observed from 2 to 15 months after injection. The plasma acetaminophen concentration, which is an indirect indicator of the gastric emptying rate, was delayed in 2 of 5 diabetic dogs from 15 months after the induction of diabetes. The effects of SK-951, a benzofuran derivative, on delayed gastric emptying were also examined in diabetic gastroparetic dogs in comparison with those of cisapride. SK-951 (1 mg/kg i.v.) significantly enhanced delayed gastric emptying in diabetic dogs, but cisapride (1 mg/kg i.v.) had no effect. In addition, SK-951 increased the plasma glucose levels in a manner correlated with its effect on gastric emptying. The present study suggested that SK-951 may be useful in the treatment of diabetic gastroparesis.

Topics: Acetaminophen; Animals; Benzofurans; Blood Glucose; Body Weight; Bridged Bicyclo Compounds, Heterocyclic; Cisapride; Diabetes Mellitus, Experimental; Dogs; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Male; Time Factors