Domperidone

Domperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-me

Severe Proarrhythmic Potential of the Antiemetic Agents Ondansetron and Domperidone.[Pubmed:28185059]

Cardiovasc Toxicol. 2017 Oct;17(4):451-457.

The potential of ondansetron and Domperidone, both clinically established antiemetic agents, to increase the QT-interval has been described in several case reports. Therefore, the aim of the present study was to investigate whether these drugs may provoke polymorphic ventricular tachycardia in a sensitive experimental model of drug-induced proarrhythmia. In 10 female rabbits, ondansetron (1, 5 and 10 microM, n = 10) or Domperidone (0.5, 1 and 2 microM, n = 8) was infused after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG reproduced the clinically observed QT-prolongation (ondansetron: 1 microM:+17 ms, 5 microM:+41 ms, 10 microM:+78 ms, p < 0.01; Domperidone: 0.5 microM:+57 ms, 1 microM:+79 ms, 2 microM:+99 ms, p < 0.01). This was accompanied by a significant increase in action potential duration at 90% of repolarization. Administration of both agents also increased dispersion of repolarization (ondansetron: 1 microM:+12 ms, 5 microM:+17 ms; 10 microM:+18 ms, p < 0.05; Domperidone: 0.5 microM:+19 ms, 1 microM:+27 ms; 2 microM:+23 ms p < 0.05). Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 9 of 10 ondansetron-treated hearts and induced polymorphic ventricular tachycardia (VT) resembling torsade de pointes in 7 of 10 ondansetron-treated hearts (86 episodes). Under the influence of Domperidone, EAD and polymorphic VT occurred in 7 of 8 hearts (131 episodes). In the present study, both ondansetron and Domperidone demonstrated a severe proarrhythmic potential. A significant prolongation of cardiac repolarization as well as a marked increase in spatial dispersion of repolarization represents the underlying electrophysiologic mechanisms. These results imply that application of ondansetron should be handled carefully. For regular administration, ECG monitoring should be mandatory.

Enhancing Human Milk Production With Domperidone in Mothers of Preterm Infants.[Pubmed:28107101]

J Hum Lact. 2017 Feb;33(1):181-187.

BACKGROUND: Mothers of preterm infants often are at risk of expressing an inadequate amount of milk for their infants and the use of galactogogues is often considered. Domperidone is a widely used galactogogue with little information available to guide clinicians regarding initiation, timing, and duration of treatment. Research aim: The primary objective of this study was to determine whether administration of Domperidone within the first 21 days after delivery would lead to a higher proportion of mothers achieving a 50% increase in the volume of milk at the end of 14 days of treatment compared with mothers receiving placebo. METHODS: Eligible mothers were randomized to one of two treatment arms: Group A-Domperidone 10 mg orally three times daily for 28 days; or Group B-placebo 10 mg orally three times daily for 14 days followed by Domperidone 10 mg orally three times daily for 14 days. RESULTS: A total of 90 mothers of infants

Management, prevention and treatment of canine leishmaniosis in north-eastern Spain: an online questionnaire-based survey in the province of Girona with special emphasis on new preventive methods (CaniLeish vaccine and domperidone).[Pubmed:27895289]

Vet Rec. 2017 Jan 14;180(2):47.

Knowledge of how canine leishmaniosis (CanL) is being managed clinically and its epidemiology is very important, since dogs are the main reservoir of human leishmaniosis. This study reports the results obtained through a questionnaire-based survey of veterinary practitioners in Girona province, a recognised, but non-documented endemic area in north-eastern Spain. The primary objective was to obtain data on the clinical management of CanL, focusing particularly on new preventive methods and therapeutic tools. The results show an extensive routine management of CanL cases and a widespread use of the CaniLeish (Virbac) vaccine and Domperidone (Leisguard, Esteve). Adverse reactions were detected by a vast majority of the vaccine users (82 per cent), the most frequent being local reactions, apathy, fever and gastroenteritis. All the respondents had treated confirmed cases, and the therapeutic protocol most used was the combination of meglumine antimoniate (Glucantime, Merial) and allopurinol (Zyloric, GlaxoSmithKline).

Should Domperidone be Used as a Galactagogue? Possible Safety Implications for Mother and Child.[Pubmed:27900667]

Drug Saf. 2017 Feb;40(2):109-113.

Domperidone has been used as a galactagogue; however, solid evidence from an adequate sized randomized clinical trial is missing. Optimal dosage, start of treatment, length of treatment and scope of patients who can benefit also remain unknown. Although milk obtained after Domperidone administration has not been shown to have untoward effects on newborns, no sufficiently large randomized clinical trial has been done to establish safety. Domperidone has repeatedly been shown to produce sudden cardiac death, starting at 30 mg/day. Because of this known cardiac effect, the use of Domperidone to increase breast milk production may not be justified.

Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets.[Pubmed:15894081]

Pharmacol Biochem Behav. 2005 May;81(1):211-9.

Agents that activate the dopamine D2-like family of receptors elicit emesis in humans and other species with a vomiting/emetic reflex; however, the lack of dopamine receptor subtype selective agonists has hampered an understanding of which dopamine D2-like receptor subtype(s) contributes to the emetic response. In this study, stable cell lines expressing the ferret dopamine D2-long (D2L) and D4 receptors were used to characterize known dopamine agonists via radioligand binding and calcium ion flux assays, while emetic activity of these dopamine receptor agonists was determined in male ferrets. Latencies to first emetic event, average number of emetic episodes, and stereotypical behaviors which may be indicative of nausea were also determined. Agonists at dopamine D1-like and D4 receptors had no emetic effect in ferrets. Conversely, stimulation of dopamine D2 and/or D3 receptors resulted in a robust emetic response characterized by a relatively short latency (<15 min) and multiple emetic events. Competitive antagonists of dopamine D2-like receptors (Domperidone, haloperidol) dose-dependently blocked the emetic response to PNU95666E, a dopamine D2 receptor selective agonist. Thus, dopamine D2 and/or D3 receptor agonists elicit emesis, while dopamine D1/D5 or D4 receptor-selective agonists are devoid of emetic properties.

Domperidone. A review of its use in diabetic gastropathy.[Pubmed:9777316]

Drugs. 1998 Sep;56(3):429-45.

UNLABELLED: Domperidone is a selective antagonist at peripheral dopamine D2 receptors, with gastroprokinetic and antiemetic properties. It increases the frequency and duration of antral and duodenal contractions, thus decreasing/improving transit time of food through the gastrointestinal tract. Gastric emptying of liquids and solids is significantly improved with oral Domperidone 40 to 120 mg/day in patients with diabetic gastropathy. Oral Domperidone 40 to 80 mg/day significantly decreased the severity of symptoms of gastropathy from baseline values in 66 to 88% of patients with type 1 (insulin-dependent) or insulin-requiring diabetes mellitus. Double-blind withdrawal of Domperidone from patients who had responded previously led to greater deterioration of symptoms in patients with delayed gastric emptying than in those who continued receiving the drug. Quality of life was significantly improved in patients who showed a symptomatic response to Domperidone. The administration of Domperidone 40 to 120 mg/day significantly reduced hospitalisation rates in patients with gastropathy. The symptomatic improvement with Domperidone 80 mg/day was similar to that seen with cisapride 40 mg/day or metoclopramide 40 mg/day, and therapeutic benefits seen in symptoms of gastropathy were maintained with Domperidone for up to 12 years. Domperidone 40 to 80 mg/day may be effective in patients who are refractory to metoclopramide, and a combination of Domperidone 80 mg/day with cisapride 80 mg/day may improve some symptoms in patients who do not respond to either agent alone. Domperidone 40 to 120 mg/day was well tolerated for periods up to 12 years in trials in patients with diabetic gastropathy. Adverse events with Domperidone 80 mg/day were similar to those seen in placebo recipients and significantly fewer than in patients receiving metoclopramide 40 mg/day. Although significant elevation of plasma prolactin levels (unrelated to dosage and duration of treatment) occurred in all Domperidone recipients, prolactin-related adverse events were observed in only 10 to 20% of patients. CONCLUSIONS: The available data suggest that Domperidone 40 to 80 mg/day is an effective agent for the management of symptoms of gastropathy in patients with type 1 diabetes mellitus. In addition, it may provide symptom improvement in patients with gastropathy refractory to other gastroprokinetic agents. Domperidone maintains efficacy in the long term (up to 12 years) and appears to have a better tolerability profile than metoclopramide 40 mg/day.

The antiemetic effects of domperidone, a novel potent gastrokinetic.[Pubmed:7416883]

Arch Int Pharmacodyn Ther. 1980 Mar;244(1):130-40.

Domperidone is the prototype of a new chemical class of compounds with potent gastrokinetic properties. The present study reports on the antiemetic activity and safety of Domperidone in dogs. The lowest ED50-values protecting from apomorphine (0.31 mg/kg s.c.) induced emesis are 0.003 mg/kg intravenously, 0.007 mg/kg subcutaneously, 0.03 mg/kg orally and 0.10 mg/kg rectally. Emesis induced by i.v. hydergine, s.c. morphine and oral levodopa is also prevented by low doses of intravenous Domperidone, whereas oral copper sulphate-induced emesis is not antagonized. The doses of Domperidone needed to induce central depressant effects in dogs (inhibition of conditioned reactions) are at least 300 times higher than the antiemetic doses (apomorphine-induced emesis). Domperidone is also devoid of sedative, adrenolytic and cardiovascular side-effects. The LD50-values in dogs are 42.7 mg/kg intravenously, and more than 160 mg/kg subcutaneously and orally.