Domperidone
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Domperidone
- Domperidone: From Prokinetic/Antiemetic Use to Nephrogenic Syndrome of Inappropriate Antidiuresis
Domperidone: From Prokinetic/Antiemetic Use to Nephrogenic Syndrome of Inappropriate Antidiuresis
One-Sentence Summary
Domperidone is a peripheral dopamine D2/D3 receptor antagonist, generally used as a prokinetic and antiemetic. The TxGNN model predicts it may be effective for nephrogenic syndrome of inappropriate antidiuresis (NSIAD), but there are currently 0 clinical trials and 0 publications supporting this direction. It is a model-derived association only, with no credible mechanistic link.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration record; generally used as a prokinetic and antiemetic |
| Predicted New Indication | Nephrogenic syndrome of inappropriate antidiuresis |
| TxGNN Prediction Score | 99.08% (model rank 4550) |
| Evidence Level | L5 (model prediction only) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the record. Domperidone is known as a peripheral dopamine D2/D3 receptor antagonist. Its established effects are on gastrointestinal motility and nausea/vomiting.
NSIAD is caused by gain-of-function mutations in AVPR2 (the vasopressin V2 receptor). These produce constitutive antidiuresis while circulating vasopressin (AVP) is suppressed. Domperidone has no known action on the V2 receptor or the aquaporin-2 pathway, so the two conditions share no obvious pharmacological link.
The high TxGNN score is a knowledge-graph association only. No trial or publication supports it, and the record lacks both original-indication data and MOA data, so the prediction cannot be cross-checked against curated pharmacology. On current information, the prediction is not mechanistically well supported.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 52/5.7.2/0563 | Domperidone Cipla | Orally disintegrating tablet (ODT) | Not stated in the record |
Safety Considerations
- Cardiac risk (from the evidence pack’s assessment): Domperidone carries a risk of QT prolongation and arrhythmia. Electrolyte disturbance such as hyponatremia, which can occur in NSIAD, could compound this risk.
- Drug Interactions: The interaction query returned no records. This does not mean there are no interactions.
Please refer to the SAHPRA-approved Professional Information (PI) for warnings, contraindications and interaction details. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a model score, with no clinical trials, no literature and no plausible mechanistic link to V2 receptor-driven antidiuresis. The known QT and arrhythmia risk, together with possible electrolyte disturbance in NSIAD, adds a safety concern with no offsetting efficacy signal.
To proceed, the following is needed:
- A credible mechanistic rationale linking dopamine D2/D3 antagonism to the AVPR2/aquaporin-2 pathway, supported by preclinical data
- Mechanism of action data for domperidone (e.g. from DrugBank)
- Original indication text and safety sections (warnings, contraindications) from the SAHPRA-approved PI
- Any published case reports or preclinical studies in NSIAD, none of which are currently identified
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.