Prucalopride

證據等級: L5

預測適應症: 10 個

Prucalopride: From Chronic Constipation to Amyloidosis-Associated Intestinal Pseudo-Obstruction

One-Sentence Summary

Prucalopride is a selective 5-HT4 receptor agonist known clinically for promoting gastrointestinal motility in chronic constipation. Among 10 TxGNN-predicted indications, only amyloidosis-related gastrointestinal dysmotility (chronic intestinal pseudo-obstruction) has any supporting literature — 2 case/review publications, no clinical trials — while the remaining 8 candidates, including the highest-scoring prediction (hypoalphalipoproteinemia), have no mechanistic or evidentiary support and are flagged as algorithmic noise.

Quick Overview

Item	Content
Original Indication	Chronic constipation (per known 5-HT4 agonist pharmacology, cited in evidence-pack rationale text; no license record available)
Predicted New Indication	Amyloidosis-associated intestinal pseudo-obstruction (rank 6, highest-evidence candidate)
TxGNN Prediction Score	99.62% (rank 9,662 of full candidate list)
Evidence Level	L4 (mechanism/case-report level only)
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data for prucalopride is not available in this evidence pack (data gap, source: DrugBank, not yet retrieved). Based on the information present in the repurposing rationale fields, prucalopride is a selective 5-HT4 receptor agonist used clinically to enhance gastrointestinal motility in chronic constipation.

Amyloid deposits can infiltrate the enteric autonomic nervous plexus, producing chronic intestinal pseudo-obstruction (CIPO) — a motility failure state. This shares a plausible pathophysiological overlap with prucalopride’s prokinetic mechanism, giving the prediction some biological rationale. However, the two supporting publications only document the clinical presentation and diagnostic challenges of amyloidosis-related CIPO; neither studies prucalopride treatment directly. This is therefore an indirect, mechanism-based hypothesis rather than treatment evidence.

By contrast, the TxGNN model’s highest-scoring prediction (hypoalphalipoproteinemia, rank 1) and six other candidates (homozygous familial hypercholesterolemia, duodenal ulcer, oral candidiasis, obsolete familial combined hyperlipidemia, strongyloidiasis, HIV infection, acquired amyloid peripheral neuropathy) have no mechanistic link, no clinical trials, and no literature. The evidence pack itself characterizes these as algorithmic noise lacking biological plausibility.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

(for amyloidosis-associated intestinal pseudo-obstruction, rank 6 — the only candidate with literature support)

PMID	Year	Type	Journal	Key Findings
40376135	2025	Case Report	Cureus	61-year-old man with chronic nausea, vomiting, and abdominal pain from recurrent small bowel dilation; extensive workup for CIPO ultimately pointed toward amyloidosis as an underlying cause, illustrating diagnostic difficulty rather than treatment outcome.
34231480	2021	Review	Turkish J Gastroenterol	Notes that specific GI motility disorders (gastroparesis, CIPO, colonic inertia) are frequently misdiagnosed as functional GI disorders in Asia due to low physician awareness; does not address prucalopride use.

A second candidate, primary (AL-type) amyloidosis (rank 9), shares the same review article (PMID 34231480) with the same limitation — descriptive of disease mechanism, not treatment evidence.

Other TxGNN-Predicted Indications (Low Confidence, Not Pursued)

The remaining 8 of 10 predictions carry TxGNN scores in a similar range (99.5–99.8%) but have no clinical trials, no literature, and no stated mechanistic link — all rated L5 / Hold:

Rank	Disease	TxGNN Score	Note
1	Hypoalphalipoproteinemia	99.82%	Highest score overall; no biological plausibility identified
2	Homozygous familial hypercholesterolemia	99.67%	No mechanistic link
3	Duodenal ulcer	99.65%	No link to Hp infection or acid secretion pathways
4	Oral candidiasis	99.64%	No plausible mechanism
5	Familial combined hyperlipidemia (obsolete term)	99.62%	Obsolete disease classification; recommend exclusion
7	Strongyloidiasis	99.60%	No antiparasitic mechanism
8	HIV infection	99.60%	No antiviral/immunomodulatory link
10	Acquired amyloid peripheral neuropathy	99.55%	Conceptually adjacent to CIPO signal but unsupported by evidence

These are listed for transparency but do not warrant further evaluation at this time.

Safety Considerations

Please refer to the package insert for safety information.

(Note: this evidence pack flags TFDA/FDA warning and contraindication data as a Blocking data gap — DG001 — preventing entry into formal safety screening (S1) for any candidate in this set.)

Conclusion and Next Steps

Decision: Hold

Rationale: Only 1 of 10 predicted indications (amyloidosis-associated intestinal pseudo-obstruction, plus its closely related primary-amyloidosis variant) has any literature support, and that support is mechanism-descriptive rather than treatment evidence — no clinical trials exist for prucalopride in this indication. The remaining candidates, including the top TxGNN-scored prediction, show no biological plausibility. Combined with missing MOA and regulatory safety data, this candidate set does not meet the bar to proceed.

To proceed, the following is needed:

TFDA/FDA label warnings and contraindications (DG001 — blocking; required before any safety screening)
Confirmed mechanism of action data from DrugBank (DG002)
Preclinical or clinical studies directly testing prucalopride in amyloidosis-related GI dysmotility (currently only disease-mechanism literature exists)
Case series or real-world evidence of prucalopride use in CIPO/amyloidosis patients, if this signal is to be pursued as a research question
Disclaimer

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