Cyclandelate
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Cyclandelate: From Peripheral Vascular Disease to Migraine Prophylaxis
One-Sentence Summary
Cyclandelate (brand name Cyclospasmol) is a peripheral vasodilator historically used for circulatory disorders such as peripheral vascular disease and intermittent claudication. Among 10 TxGNN-predicted indications, migraine disorder stands out as the best-supported candidate, with a TxGNN score of 99.69% and 6 randomized controlled trials (13 publications total) directly evaluating cyclandelate for migraine prophylaxis — making it the only candidate in this evidence pack that clears an L2 evidence bar.
(Note: this drug generated 10 TxGNN-predicted indications. This report focuses on the strongest-evidenced one, migraine disorder. A summary of the other 9 lower-priority candidates appears near the end.)
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Peripheral Vascular Disease / circulatory disorders (historical, brand name Cyclospasmol) — no structured Taiwan/India license record exists |
| Predicted New Indication | Migraine disorder |
| TxGNN Prediction Score | 99.69% (rank 5,863 of candidates) |
| Evidence Level | L2 |
| India Market Status | ✗ Not marketed |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, no formal DrugBank/regulatory mechanism-of-action record is available for cyclandelate (flagged as a data gap in this evidence pack). Based on the pharmacological description found in the supporting literature (PMID 8902255), cyclandelate inhibits calcium-induced contraction of vascular smooth muscle, inhibits platelet aggregation induced by thrombin, platelet-activating factor and adenosine, and suppresses provoked serotonin (5-HT) release from platelets. This places it functionally alongside calcium-channel-blocking migraine prophylactics such as flunarizine.
Cyclandelate’s original use was as a peripheral/cerebral vasodilator for circulatory disorders (Cyclospasmol). Migraine pathophysiology involves both vascular (cortical spreading depression, vasospasm) and serotonergic mechanisms — both of which overlap with cyclandelate’s known pharmacology. This mechanistic bridge is why cyclandelate was actually studied and used as a migraine prophylactic agent in several European countries during the 1980s–1990s, predating this TxGNN prediction by decades — i.e., the model’s high score recovers a real, previously established clinical use rather than a purely novel hypothesis.
It’s worth noting the evidence is mixed: several earlier RCTs (1987–1998) reported positive prophylactic effects comparable to propranolol, pizotifen, and flunarizine, but the largest and most recent placebo-controlled trial (PMID 11298666, 2001, n=251) failed to meet its primary endpoint. This tempers the otherwise favorable historical signal.
Clinical Trial Evidence
Currently no related clinical trials registered on ClinicalTrials.gov or ICTRP.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1573338 | 1992 | RCT | Journal of Medicine | Double-blind study (n=61 after run-in) comparing cyclandelate vs. pizotifen for migraine prophylaxis over 12 weeks; comparable efficacy and tolerance |
| 8902255 | 1996 | RCT | Cephalalgia | Multicentre double-blind study (n=214) vs. placebo and propranolol; cyclandelate’s calcium-antagonist profile supports prophylactic potential |
| 9584874 | 1998 | RCT | Functional Neurology | Double-blind placebo-controlled study using contingent negative variation (CNV) to probe central mechanisms of cyclandelate in migraine |
| 11298666 | 2001 | RCT | Cephalalgia | Largest trial (n=251), multicentre placebo-controlled; primary endpoint (reduction in migraine days) not met — negative result |
| 7649498 | 1995 | RCT | Functional Neurology | Double-blind study vs. propranolol and placebo; responder/non-responder analysis of cyclandelate’s prophylactic effect |
| 3304950 | 1987 | RCT | Drugs | Double-blind trial (n=40) comparing cyclandelate 800mg BID vs. flunarizine 5mg; both significantly reduced migraine symptoms vs. baseline |
| 9829155 | 1998 | Review | Drugs | Practical guide to migraine management and prevention, contextualizing prophylactic agents including calcium antagonists |
| 10463349 | 1999 | Review | Journal of Neurology | Overview of antimigraine drug treatment options for acute attacks and prophylaxis |
| 9139407 | 1997 | Review | Therapeutische Umschau | Migraine diagnosis, differential diagnosis and therapy overview |
India Market Information
Cyclandelate is not currently marketed in India — 0 registered licenses on file. No dosage form, brand name, or approved indication text is available for this market.
Safety Considerations
Please refer to the package insert for safety information.
No structured key warnings, contraindications, or drug-drug interaction (DDI) data were retrievable for cyclandelate in this evidence pack — the TFDA-equivalent label lookup returned no results, and the local DDI database file was unavailable at query time. This is flagged as a Blocking data gap in the evidence pack (DG001): safety data must be obtained before this candidate can pass the initial safety screening stage.
Other Predicted Indications (Screened, Lower Priority)
For completeness, the remaining 9 TxGNN-predicted indications for cyclandelate in this evidence pack, ranked by model score:
| Rank | Disease | TxGNN Score | Evidence Level | Recommendation |
|---|---|---|---|---|
| 1 | Prinzmetal angina | 99.80% | L5 | Hold (no clinical/literature evidence) |
| 2 | Raynaud disease | 99.73% | L4 | Research Question (1 old case-series report only) |
| 4 | Migraine with brainstem aura | 99.62% | L4 | Research Question (indirect qEEG studies, not subtype-specific) |
| 5 | Pulmonary hypertension | 99.50% | L5 | Hold (no evidence) |
| 6 | Gout | 99.43% | L5 | Hold (no mechanistic rationale, likely graph noise) |
| 7 | Kyphoscoliotic heart disease | 99.36% | L5 | Hold (no evidence) |
| 8 | Benign prostatic hyperplasia | 99.08% | L5 | Hold (cyclandelate is not an alpha-blocker; no evidence) |
| 9 | Exostosis | 99.06% | L5 | Hold (no mechanistic plausibility, likely graph noise) |
| 10 | Peripheral vascular disease | 99.04% | L3 | Hold (this drug’s original historical indication, but pivotal 1984 RCT was negative) |
Notably, rank 10 (peripheral vascular disease) is cyclandelate’s original indication as Cyclospasmol — and the key RCT (PMID 6364892) found no effect, which is a useful sanity check on how much weight to give TxGNN scores alone without evidence triangulation.
Conclusion and Next Steps
Decision: Proceed with Guardrails (for the migraine disorder indication)
Rationale: Migraine prophylaxis is the only indication in this candidate’s prediction set with L2 evidence (multiple historical RCTs), reflecting a genuine, previously-established off-label/international use rather than a purely computational artifact. However, the largest and most recent trial (2001) was negative, and the drug is not currently marketed in India, so this is not a “Go” without further work.
To proceed, the following is needed:
- Obtain formal safety/label data (DG001, Blocking) — key warnings, contraindications, and DDI profile currently have no source
- Formal DrugBank/mechanism-of-action confirmation (DG002, High) to properly ground the mechanistic rationale
- A structured comparison of the positive (1987–1998) vs. negative (2001) trial results to assess whether efficacy is dose-, population-, or subtype-dependent
- Confirmation of import/registration pathway feasibility, since cyclandelate has zero current registrations in India
- The 9 lower-priority predictions (Prinzmetal angina, Raynaud disease, etc.) should remain on Hold pending any new clinical trial or literature signal — no further action needed unless new evidence emerges
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.