Metoclopramide
| 證據等級: L5 | 預測適應症: 5 個 |
目錄
Metoclopramide: From Nausea, Vomiting and Gastroparesis to Gastric Ulcer
One-Sentence Summary
Metoclopramide is a dopamine D2-receptor antagonist internationally used for nausea, vomiting and gastroparesis (its formal South African licensing status could not be confirmed — it is currently not marketed locally). The TxGNN model predicts it may be effective for Gastric Ulcer, but supporting evidence is thin: only 2 clinical trials (neither designed to treat ulcers) and 20 publications, most of which are decades-old preclinical or mechanistic studies rather than disease-specific efficacy data.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Nausea, vomiting and gastroparesis (internationally established use; not derivable from South African licensing data, as the drug has 0 SAHPRA registrations on record) |
| Predicted New Indication | Gastric Ulcer |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| 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 the evidence pack. Based on known pharmacology, metoclopramide is a dopamine D2-receptor antagonist with two principal effects: a central antiemetic action (blocking the medullary chemoreceptor trigger zone) and a peripheral prokinetic action (increasing gastric emptying and lower oesophageal sphincter tone via dopamine antagonism and enhanced acetylcholine release). It has no acid-suppressing or mucosal-protective activity — the two mechanisms that underlie standard gastric ulcer therapy (e.g., PPIs, H2-blockers, sucralfate).
Gastric ulcer and metoclopramide’s established indications (gastroparesis, GERD-related motility disorders, chemotherapy/surgery-related nausea) both involve the upper gastrointestinal tract, which likely explains the TxGNN model’s high similarity score — the knowledge graph associates the drug with anatomically and symptomatically adjacent GI conditions. However, the underlying evidence base does not support a therapeutic (ulcer-healing) mechanism: several preclinical rodent studies (below) suggest an indirect “ulcer-protective” effect via improved gastric drainage and reduced pyloric reflux, independent of acid secretion, but this has not been translated into any completed disease-specific human trial.
Reflecting this, the two identified clinical trials do not test metoclopramide as an ulcer treatment — one is a pharmacist-led prescribing-safety quality improvement study, and the other evaluates pre-endoscopy use to improve visualization in active GI bleeding, not ulcer healing itself.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03747107 | N/A | Completed | 19 | Pharmacist- and data-driven prescribing safety quality improvement programme in primary care (Scotland); not a gastric ulcer treatment trial — low relevance (grade C). |
| NCT05746377 | Phase 4 | Unknown | 60 | Tests whether pre-endoscopy metoclopramide improves gastric visibility and reduces need for repeat intervention in upper GI bleeding; evaluates a procedural adjunct, not ulcer healing — status unknown, no published results (grade B). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 775822 | 1976 | Clinical study | ZFA. Zeitschrift für Allgemeinmedizin | Reports on therapy of gastric and duodenal ulcer with metoclopramide (abstract not available). |
| 19225 | 1977 | Review | Drugs | General review of drug treatments for gastric and duodenal ulcer (abstract not available). |
| 2730234 | 1989 | Animal study | Arch Int Pharmacodyn Ther | Metoclopramide (20–50 mg/kg) produced an ulcer-protective effect in aspirin-induced and pylorus-ligated rat models, comparable to ranitidine. |
| 6436177 | 1984 | Animal study | Indian J Physiol Pharmacol | Protected against experimentally induced gastric ulceration in guinea pigs without affecting acid secretion — effect attributed to improved gastric drainage, not mucosal healing. |
| 6336644 | 1983 | Review | Annals of Internal Medicine | Pharmacology review: dopamine antagonism drives antiemetic and GI-stimulatory effects; no acid-suppressive or mucosal-protective mechanism described. |
| 16807979 | 2006 | RCT (double-blind) | Yonsei Medical Journal | IV metoclopramide plus ranitidine reduced preoperative gastric contents vs. placebo in day-case surgery patients; not disease-specific to ulcer. |
| 4779253 | 1973 | Clinical study | Current Medical Research and Opinion | Examined bile reflux in gastric ulcer patients and the effect of smoking, metoclopramide and carbenoxolone sodium (abstract not available). |
| 797497 | 1976 | Review | Clinical Pharmacokinetics | Reviews how gastric ulcer and other conditions/drugs alter gastric emptying and downstream drug absorption. |
| 28652516 | 2017 | Animal study | J Smooth Muscle Res | Studied effects of prokinetic drugs, including metoclopramide, on gastric emptying after acetic-acid-induced ulceration in rats; found regional differences by ulcer site. |
| 6106882 | 1980 | Review | Medizinische Klinik | German-language review on conservative (non-surgical) treatment of gastric ulcer (abstract not available). |
South Africa Market Information
No SAHPRA registration for metoclopramide is recorded in the evidence pack (0 licenses; market status: Not Marketed). Local product/dosage-form data could not be extracted.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
(Note: original evidence pack flags TFDA label warnings/contraindications as a Blocking data gap — this must be resolved before any safety review can proceed.)
Conclusion and Next Steps
Decision: Hold
Rationale:
- The mechanistic link is weak: metoclopramide has no acid-suppressive or mucosal-protective action, the standard mechanisms for gastric ulcer treatment. Supporting evidence is limited to preclinical rodent/guinea-pig studies and clinical trials that were not designed to test ulcer treatment (procedural/QI studies), yielding an evidence level of only L4.
- No completed Phase 2/3 RCT directly evaluates metoclopramide for gastric ulcer therapy.
To proceed, the following is needed:
- TFDA/SAHPRA-approved Professional Information (warnings, contraindications) — currently a Blocking data gap (DG001)
- Detailed mechanism of action (MOA) data from DrugBank — currently a High-severity gap (DG002)
- A disease-specific clinical trial or observational study directly testing gastric ulcer healing endpoints
- Confirmation of South African regulatory/marketing pathway, since the drug currently has no SAHPRA registration
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.