levosulpiride and Gastroparesis

The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies.. The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included.. Studies were identified for metoclopramide (n=6), domperidone (n=6), cisapride (n=14), erythromycin (n=3), botulinum toxin (n=2), and levosulpiride (n=3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors.. In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.

Topics: Cisapride; Diabetes Mellitus, Type 2; Domperidone; Erythromycin; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Metoclopramide; Severity of Illness Index; Sulpiride; Treatment Outcome

Levosulpiride is a sulpiride isomer that exerts its prokinetic action through a dual mechanism: 1) as a D(2) dopamine receptor antagonist and 2) as a serotonin 5HT(4) receptor agonist, conferring this drug with a cholinergic effect. At a dosage of 25mg three times daily, levosulpiride accelerates gastric and gallbladder emptying. Clinical trials have shown that this agent is more effective than placebo in reducing the symptoms of dyspepsia, while comparative studies have demonstrated that its effect is similar or superior to that of other dopamine antagonists. The safety profile of levosulpiride is good and the frequency of adverse events is similar to that of other D(2) dopamine antagonists. Therefore, this drug is a useful therapeutic option in the management of patients with functional dyspepsia, as well as in those with delayed gastric emptying.

Topics: Animals; Clinical Trials as Topic; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Drug Evaluation, Preclinical; Dyspepsia; Gallbladder Emptying; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Guinea Pigs; Humans; Molecular Structure; Serotonin 5-HT4 Receptor Agonists; Sulpiride

Topics: Adult; Blood Glucose; Breath Tests; Cisapride; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Hyperglycemia; Kinetics; Male; Middle Aged; Receptors, Dopamine D2; Sulpiride

The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well-established in patients with functional dyspepsia, but formal studies comparing different prokinetic drugs are lacking.. To compare the effects of chronic oral administration of cisapride and levosulpiride in patients with functional dyspepsia and delayed gastric emptying.. In a double-blind crossover comparison, the effects of a 4-week administration of levosulpiride (25 mg t.d.s.) and cisapride (10 mg t.d.s.) on the gastric emptying rate and on symptoms were evaluated in 30 dyspeptic patients with functional gastroparesis. At the beginning of the study and after levosulpiride or cisapride treatment, the gastric emptying time of a standard meal was measured by 13C-octanoic acid breath test. Gastrointestinal symptom scores were also evaluated.. The efficacy of levosulpiride was similar to that of cisapride in significantly shortening (P < 0.001) the t1/2 of gastric emptying. No significant differences were observed between the two treatments with regards to improvements in total symptom scores. However, levosulpiride was significantly more effective (P < 0.01) than cisapride in improving the impact of symptoms on the patients' every-day activities and in improving individual symptoms such as nausea, vomiting and early postprandial satiety.. The efficacy of levosulpiride and cisapride in reducing gastric emptying times with no relevant side-effects is similar. The impact of symptoms on patients' everyday activities and the improvement of some symptoms such as nausea, vomiting and early satiety was more evident with levosulpiride than cisapride.

Topics: Activities of Daily Living; Administration, Oral; Adult; Aged; Anti-Ulcer Agents; Cisapride; Cross-Over Studies; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Male; Middle Aged; Satiation; Sulpiride

We evaluated the effect of chronic administration of levosulpiride, a prokinetic drug that is a selective antagonist for D2 dopamine receptors, on the glycemic control of IDDM subjects.. The study was performed on 40 long-standing IDDM subjects with clinical signs of autonomic neuropathy and delayed gastric emptying. Gastric emptying time and glycemic parameters (diurnal glycemic profile and HbA1c) were checked under double-blind conditions before and after the administration of levosulpiride at the dosage of 25 mg t.i.d. orally for 6 months, or placebo.. No significant differences were noted in the glycemic and HbA1c values before and after 6 months of placebo administration. In contrast, after 6 months of levosulpiride, glycemic control had improved (HbA1c 6.7 +/- 0.4 and 5.7 +/- 0.3%, P < 0.01; mean daily glycemia 10.9 +/- 0.8 and 8.8 +/- 0.4 mmol/l, P < 0.05, at the start and at the end of the study), while the dosage of injected insulin (0.65 +/- 0.02 IU.kg-1.day-1) and the number of severe hypoglycemic episodes remained unchanged. After 6 months of levosulpiride therapy, the time of gastric emptying was significantly reduced from 321 +/- 14 to 261 +/- 9 min (P < 0.001) and dyspeptic symptoms had improved.. Our results show the importance of gastric emptying in the maintenance of glycemic control and the usefulness of chronic administration of levosulpiride in diabetic subjects with gastroparesis.

Topics: Administration, Oral; Adult; Autonomic Nervous System Diseases; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Dopamine Antagonists; Double-Blind Method; Female; Gastric Emptying; Gastroparesis; Glycated Hemoglobin; Humans; Male; Middle Aged; Sulpiride; Time Factors

Antidopaminergic drugs may be useful in diabetic gastroparesis because the inhibitory activity of hyperglycemia on gastric motility seems to be related to dopamine receptor stimulation. For this reason, we evaluated the effect of levosulpiride on gastric emptying, dyspeptic symptoms, and metabolic parameters of insulin-treated diabetic patients.. Under double-blind conditions, 40 longstanding, insulin-treated dyspeptic patients with autonomic neuropathy and delayed gastric emptying were randomly submitted, with an interval of 15 days, to 4 wk of administration of both levosulpiride 25 mg t.i.d. and placebo according to a cross-over design. At the beginning of the study and after levosulpiride or placebo treatment, the gastric emptying time of a standard meal was measured ultrasonically; gastrointestinal symptom scores and glycaemic control were also evaluated.. Levosulpiride reduced significantly (p < 0.001) the gastric emptying time from 416 +/- 58 to 322 +/- 63 min, whereas placebo did not change it consistently (396 +/- 58 vs 372 +/- 72 min). Symptoms improved significantly (p < 0.001) with levosulpiride compared with placebo. However, there was no significant correlation between the acceleration of gastric emptying and the symptomatological improvement. The reduction of mean plasma glycosylated hemoglobin concentrations after levosulpiride (7.3 +/- 1.9 vs 5.8 +/- 1.3) was not significantly different (p = not significant) compared with placebo (6.8 +/- .7 vs 6.1 +/- 1.4).. Our study first demonstrates that levosulpiride has an accelerating effect on the emptying of solids from the stomach of patients with diabetic gastroparesis. The drug is also effective in relieving upper gastrointestinal symptoms in patients whose gastric emptying times remain very slow. Our findings suggest, but do not prove, that better blood glucose control could be achieved with reduction of gastric emptying time; further trials are needed in this field.

Topics: Cross-Over Studies; Diabetes Mellitus, Type 1; Dopamine Antagonists; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Glycated Hemoglobin; Humans; Male; Middle Aged; Sulpiride; Time Factors

Gastroparesis is a well-known consequence of long-standing diabetes that presents with gastric dysmotility in the absence of gastric outlet obstruction. This study aimed to evaluate the therapeutic effects of mosapride and levosulpiride on improving gastric emptying in type 2 diabetes mellitus (T2DM) while regulating glycemic levels.. Rats were divided into the normal control, untreated diabetic, metformin-treated (100 mg/kg/day), mosapride-treated (3 mg/kg/day), levosulpiride-treated (5 mg/kg/day), metformin (100 mg/kg/day) + mosapride (3 mg/kg/day)-treated, and metformin (100 mg/kg/day) + levosulpiride (5 mg/kg/day)-treated diabetic groups. T2DM was induced by a streptozotocin-nicotinamide model. Fourweeks from diabetes onset, the treatment was started orally daily for 2 weeks. Serum glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels were measured. Gastric motility study was performed using isolated rat fundus and pylorus strip preparations. Moreover, the intestinal transit rate was measured.. Mosapride and levosulpiride administration showed a significant decrease in serum glucose levels with improvement of gastric motility and intestinal transit rate. Mosapride showed a significant increase in serum insulin and GLP-1 levels. Metformin with mosapride and levosulpiride co-administration showed better glycemic control and gastric emptying than either drug administered alone.. Mosapride and levosulpiride showed comparable prokinetic effects. Metformin administration with mosapride and levosulpiride showed better glycemic control and prokinetic effects. Mosapride provided better glycemic control than levosulpiride. Metformin + mosapride combination provided superior glycemic control and prokinetic effects.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Gastroparesis; Glucagon-Like Peptide 1; Glycemic Control; Insulins; Metformin; Rats

To investigate if diabetes is more common in drug-induced parkinsonism patients. We performed a hospital-based retrospective case-control study on 44 drug-induced parkinsonism (DIP) patients, 177 Parkinson disease patients, and 176 acute stroke patients matched for age and sex who were seen over the same period at the same hospital. The frequency of diabetes, age-at onset and sex were compared between DIP and IPD or acute stroke. Multivariate analysis showed that patients with diabetes are more frequent in DIP compared with IPD (p<0.001, adjusted OR 5.48; 95% CI, 2.52-11.94). The frequency of diabetes in DIP was comparable to that in acute stroke patients (p=0.16, adjusted OR 0.62; 95% CI, 0.32-1.21). These data suggest that diabetes may be a risk factor for DIP. Drugs with dopamine receptor blocking potency should be avoided in elderly with diabetes.

Topics: Age of Onset; Aged; Contraindications; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Susceptibility; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Female; Gastroparesis; Humans; Male; Middle Aged; Parkinsonian Disorders; Retrospective Studies; Risk Factors; Sex Distribution; Single-Blind Method; Stroke; Sulpiride