Imidapril
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Imidapril: From Hypertension to Pulmonary Hypertension (Multifactorial)
One-Sentence Summary
Imidapril is an ACE inhibitor originally used to treat hypertension. The TxGNN model predicts it may be useful for pulmonary hypertension with unclear multifactorial mechanism, but this is a computational prediction only, with 0 clinical trials and 0 publications specific to this indication. The closest supporting evidence in the data compiled for this report is preclinical work in cerebrovascular disease models (see the note on other predicted indications below).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (hypertensive disorder) |
| Predicted New Indication | Pulmonary hypertension with unclear multifactorial mechanism |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Imidapril is known to be an angiotensin-converting enzyme (ACE) inhibitor; the pharmacology record lists ACE (gene ACE, human) as its target. ACE inhibition reduces angiotensin II production, which lowers vasoconstriction and may limit vascular remodelling.
Because hypertension is driven partly by this pathway, and angiotensin II signalling also plays a role in pulmonary vascular tone and remodelling, a theoretical link to pulmonary hypertension exists. The high TxGNN score likely reflects shared vascular and hypertension biology in the knowledge graph.
However, this is a plausibility argument only. No trials or publications were found for imidapril in this indication, and ACE inhibitors have not shown established benefit in pulmonary hypertension.
Other predicted indications (for context):
| Rank | Predicted Indication | Score | Evidence Level | Decision |
|---|---|---|---|---|
| 2 | Pulmonary hypertension owing to lung disease and/or hypoxia | 99.78% | L5 | Hold |
| 3 | Malignant renovascular hypertension | 99.76% | L5 | Hold |
| 4 | Malignant hypertensive renal disease | 99.76% | L5 | Hold |
| 5 | Braddock syndrome | 99.70% | L5 | Hold |
| 6 | Chronic pulmonary heart disease | 98.33% | L5 | Hold |
| 7 | Cerebrovascular disorder | 95.79% | L4 | Research Question |
| 8 | Spinal cord ischemia | 80.70% | L5 | Hold |
| 9 | Intracerebral haemorrhage | 77.49% | L4 | Hold |
| 10 | Brain stem infarction | 76.38% | L5 | Hold |
Cerebrovascular disorder is the only prediction with a meaningful body of imidapril-specific evidence, all of it preclinical. Malignant renovascular hypertension and malignant hypertensive renal disease have the strongest mechanistic rationale (RAAS-driven, close to the original indication), but no direct evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for the primary predicted indication (pulmonary hypertension).
For reference, the literature found for the best-supported alternative prediction, cerebrovascular disorder, is summarised below (all but one are animal studies):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22983755 | 2012 | Meta-analysis (ACE inhibitor class) | Advances in Therapy | Meta-analysis of five Asian studies on ACE inhibitors for preventing post-stroke pneumonia; class effect, not imidapril-specific |
| 21937941 | 2012 | Preclinical (animal) | Neurosurgery | Imidapril inhibited cerebral aneurysm formation via an ACE-independent, MMP-9-dependent mechanism |
| 8421827 | 1993 | Preclinical (animal) | Stroke | Prophylactic effect of imidapril on stroke in stroke-prone hypertensive rats, compared with enalapril |
| 7963504 | 1994 | Preclinical (animal) | Journal of Hypertension | MRI showed therapeutic effects of imidapril on cerebral lesions in malignant stroke-prone hypertensive rats |
| 10456289 | 1999 | Preclinical (animal) | Fundamental & Clinical Pharmacology | Post-stroke imidapril reduced learning deficits and brain oedema in stroke-prone rats |
| 10823269 | 2000 | Preclinical (animal) | Thrombosis and Haemostasis | Imidapril protected against laser-induced cerebral thrombosis in stroke-prone rats |
| 7869607 | 1994 | Preclinical (animal) | Japanese Journal of Pharmacology | Histopathology in salt-loaded stroke-prone rats whose renal dysfunction markers improved with imidapril |
| 8437371 | 1993 | Preclinical (animal) | Japanese Journal of Pharmacology | Imidapril improved salt-loading-induced biochemical abnormalities and reduced stroke incidence without lowering blood pressure |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10614P | TANATRIL TABLETS 10 mg | Tablet | Not stated in the available data |
| SIN10615P | TANATRIL TABLETS 5 mg | Tablet | Not stated in the available data |
Both are single-ingredient, valid licences held by PT Mitsubishi Tanabe Pharma Indonesia, for oral use.
Safety Considerations
Specific package insert warnings and contraindications were not available. Please refer to the package insert for safety information.
Points drawn from the predicted-indication assessments:
- Drug interactions: The only interaction record is the pharmacological target interaction with angiotensin-converting enzyme (its intended target). No drug-drug interactions are listed.
- Hypotension: Systemic vasodilation or hypotension could be a concern in hypoxic patients (pulmonary hypertension due to lung disease) and in acute ischaemic settings such as spinal cord ischaemia.
- Renal function: ACE inhibitors carry a known risk of acute renal function decline in bilateral renal artery stenosis, which needs careful evaluation if renovascular hypertension is pursued.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score for pulmonary hypertension is very high (99.78%), but it is a model prediction with no supporting trials or literature, and ACE inhibitors have not shown established benefit in this condition. Imidapril is already marketed in Singapore, which would ease any future work, but evidence does not yet justify moving forward.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Singapore products (currently a blocking gap for safety screening)
- Detailed mechanism of action data
- Systematic literature search for imidapril or ACE inhibitors in pulmonary hypertension
- Consideration of better-supported directions: cerebrovascular disorder (L4, preclinical evidence only; needs human studies) and RAAS-driven malignant hypertension-related conditions (strong mechanistic rationale but no direct evidence)
- A safety evaluation covering hypotension in hypoxic patients and renal risk in renovascular disease
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.