Domperidone

證據等級: L5

預測適應症: 1 個

Domperidone: From Nausea and Vomiting to Nephrogenic Syndrome of Inappropriate Antidiuresis

One-Sentence Summary

Domperidone is a peripheral dopamine D2/D3 receptor antagonist, widely used as an antiemetic and prokinetic agent for nausea, vomiting, and gastroparesis. The TxGNN model predicts it may be effective for Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD), with no clinical trials and no published literature currently supporting this specific direction — making this a model-only prediction at this stage.

Quick Overview

Item	Content
Original Indication	Nausea, vomiting, and gastroparesis (dopamine antagonist / prokinetic)
Predicted New Indication	Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD)
TxGNN Prediction Score	99.08%
Evidence Level	L5
South Africa Market Status	Not Marketed
Number of SAHPRA Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this Evidence Pack. Based on known pharmacology, domperidone is a peripheral dopamine D2 and D3 receptor antagonist that acts primarily at the gut wall and the area postrema (chemoreceptor trigger zone), which lies outside the blood-brain barrier. Its established efficacy in nausea, vomiting, and delayed gastric emptying is well documented.

Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) is a rare X-linked disorder caused by gain-of-function mutations in the AVPR2 gene (encoding the renal vasopressin V2 receptor), resulting in constitutive receptor activation, excessive water retention, and dilutional hyponatraemia — even in the absence of elevated arginine vasopressin (AVP/ADH) levels. The mechanistic rationale linking domperidone to NSIAD is indirect: dopaminergic pathways are known to modulate tubular water reabsorption and AVP secretion, and D2 receptor activity has been implicated in renal electrolyte handling. By blocking peripheral D2/D3 receptors, domperidone could theoretically influence this regulatory axis.

However, the connection between a prokinetic antiemetic and a rare renal channelopathy is not well established in clinical or preclinical literature. The TxGNN knowledge graph model captures network-level relationships between drug targets and disease nodes that may not yet have direct experimental validation. This prediction should therefore be treated as a hypothesis-generating signal requiring independent mechanistic and clinical verification before any repurposing strategy is considered.

Clinical Trial Evidence

Currently no related clinical trials registered (ClinicalTrials.gov, ICTRP, SANCTR, PACTR).

Literature Evidence

Currently no related literature available (PubMed search: domperidone AND nephrogenic syndrome of inappropriate antidiuresis returned 0 results as of 2026-04-20).

South Africa Market Information

Domperidone currently holds no SAHPRA registrations and is not marketed in South Africa according to available regulatory data.

Note: Domperidone is registered and widely used in numerous other jurisdictions (e.g., EU, Canada, Australia, UK) under brand names such as Motilium. Its absence from the SAHPRA register does not reflect a global safety withdrawal — it may reflect an unsubmitted or lapsed registration. Prescribers should verify current SAHPRA status directly before any use.

Safety Considerations

Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.

Important context for prescribers: Although formal safety data was not available in this Evidence Pack, domperidone carries a well-known class-level concern regarding QT interval prolongation and an increased risk of serious cardiac arrhythmia (including sudden cardiac death), particularly at higher doses and in patients with pre-existing cardiac risk factors or those taking concomitant QT-prolonging medications. The European Medicines Agency (EMA) and Health Canada have issued risk minimisation measures on this basis. These warnings should be carefully considered in any repurposing evaluation.

Conclusion and Next Steps

Decision: Hold

Rationale: There is currently zero clinical or preclinical evidence linking domperidone to Nephrogenic Syndrome of Inappropriate Antidiuresis; the prediction is based entirely on the TxGNN knowledge graph model (L5 evidence), and domperidone is not registered with SAHPRA, meaning a full regulatory dossier would be required before any South African clinical use.

To proceed, the following is needed:

Mechanistic validation: Commission a targeted literature and expert review to determine whether dopamine D2/D3 receptor antagonism has any plausible, experimentally supported effect on AVPR2 constitutive activity or renal water handling in NSIAD models
Preclinical evidence: Identify or initiate in vitro / in vivo studies in NSIAD cell lines or animal models (e.g., AVPR2 gain-of-function knock-in mice) to test domperidone’s effect on aquaporin-2 trafficking and urinary osmolality
Safety dossier: Retrieve and review domperidone’s SAHPRA (or EMA/Health Canada) full Professional Information for contraindications, QT-risk profile, and drug interaction data to assess suitability for a renally impaired or electrolyte-disturbed patient population
SAHPRA registration pathway: Given zero current SAHPRA registrations, a Section 21 (unregistered medicine) application or full registration submission would be required before any investigational or compassionate use in South Africa
Patient population consideration: NSIAD is an ultra-rare disease (primarily affecting neonatal/paediatric males); any development plan must account for paediatric pharmacokinetics and the specific cardiac safety concerns associated with domperidone in this age group

This report is generated for research and clinical decision-support purposes only. It does not constitute medical advice or a recommendation for off-label prescribing. All repurposing candidates require clinical validation before therapeutic use. Adverse drug reactions should be reported to SAHPRA via the MedSafety reporting system.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.