DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for migraine disorder — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMigraine disorder maps to a 47-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside migraine disorder in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of the chimeric protein of 5-HT1B-BRIL — Ergotamine Tartrate has a real, experimentally solved structure in complex with this target (PDB 4IAR, 2.7 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet ermdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4IAR · 2.7 Å · ligand Ergotamine Tartrate (ERM). Experimental structure, not a prediction.
What the evidence adds up to
In a 1995 multicentre trial, 107 patients were randomised 2:1 to divalproex or placebo. During the 12-week treatment phase, mean migraine frequency per four weeks was 3.5 in the divalproex group and 5.7 in the placebo group, compared with 6.0 and 6.4 at baseline. Forty-eight percent of divalproex patients and 14% of placebo patients had at least a 50% reduction in frequency. Treatment was stopped for intolerance in 13% of the divalproex group and 5% of the placebo group. A 2000 retrospective paediatric study of 42 patients aged 7 to 16 reported that after four months of divalproex, 78.5% had a 50% reduction in headache frequency, 14.2% had a 75% reduction, and 9.5% became headache-free. No placebo control was used.
Methysergide was introduced as the first migraine preventive agent and shifted thinking away from migraine as a psychological condition. A 1963 study of 421 patients who had failed other treatments gave methysergide at 6 to 16 mg per day for up to 29 months; the authors concluded it had no value for acute attacks but was effective for prophylaxis of all forms of migraine. A 1985 reanalysis of a comparative trial found that patients with fewer headache days per month and those with symptoms of cerebral disturbance before or during migraine had the best outcome. A 2016 survey of International Headache Society members found that 71.3% had ever prescribed methysergide and 79.8% would prescribe it if available; respondents used it more for cluster headache than migraine and reserved it for refractory patients. The European Medicines Agency had investigated methysergide due to safety concerns.
Ergotamine tartrate has been used for acute migraine attacks since at least the 1930s. A 1938 review noted that among more than 300 reported cases, approximately 90% obtained prompt relief, but also reported 42 serious sequelae following its use. A 1987 review described a syndrome of ergotamine dependency that develops when usage exceeds two or three days per week, characterised by a self-sustaining cycle of daily or near-daily headache and compulsive use of the drug. The review recommended restricting use to two days per week.
A 2013 review noted that migraine prevention remains underused despite being instrumental in management, and that optimal success requires a strong therapeutic alliance and continued education of both patient and provider. What is still missing are adequately powered, placebo-controlled trials in children for divalproex, a clear understanding of which patient subgroups benefit most from methysergide without unacceptable toxicity, and trial designs that can separate the effects of ergotamine withdrawal from those of any new prophylactic agent in patients who have developed medication-overuse headache.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 1995 · 327 citations
Migraine Prophylaxis With Divalproex
AbstractOBJECTIVE: To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache. DESIGN: Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance). SETTING: Eight headache/neurology clinics throughout the United States. PATIENTS: One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo. INTERVENTION: Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L. MEASUREMENTS AND MAIN RESULTS: During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group (p < or = .001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase (P < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant). CONCLUSIONS: Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.
Headache The Journal of Head and Face Pain · 2000 · 119 citations
The Efficacy of Divalproex Sodium in the Prophylactic Treatment of Children With Migraine
AbstractOBJECTIVE: To determine the beneficial use of divalproex sodium as a prophylactic treatment for migraine in children. BACKGROUND: Previous studies for treatment of migraine in adults have shown a greater than 50% reduction in migraine attack frequencies. Few data exist, however, regarding the efficacy and safety of divalproex sodium use in children with migraine. METHODS: We studied the incidence of headache relief in our patients with migraine aged 16 years and younger treated with divalproex sodium prophylactically at our institution from July 1996 to December 1998 to determine medication dosage used, concomitant headache medications, and possible adverse effects. RESULTS: A total of 42 patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated with divalproex sodium for headache. All had a history of migraine with or without aura. Baseline headache frequency during a minimum 6-month period was one to four headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to 45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their abortive medications. After 4 months' treatment, 50% headache reduction was seen in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients became headache-free. CONCLUSION: These results indicate divalproex sodium to be an effective and well-tolerated treatment for the prophylaxis of migraine in children.
Headache The Journal of Head and Face Pain · 1987 · 82 citations
Ergotamine Dependency‐ a Review
AbstractSYNOPSIS Ergotamine tartrate has been recognized as the drug of first choice for the treatment of acute attacks of migraine. This paper draws attention to a common but poorly delineated state of addiction that can develop when ergotamine tartrate usage exceeds two or three days per week. This syndrome is characterized by a self‐sustaining, rhythmic headache/medication cycle, with daily or almost daily migraine headaches and the irresistible and predictable use of ergotamine tartrate as the only means of alleviating the headache attacks. This report further delineates the clinical features, criteria for recognition, and treatment alternatives for this syndrome. In order to avoid this condition, usage should be restricted to 2 days per week.
COMPLICATIONS FOLLOWING THE USE OF ERGOTAMINE TARTRATE
AbstractIn the past five years ergotamine tartrate<sup>1</sup>has been used by an increasing number of physicians as an effective means of aborting or terminating migraine headache. More than 300 cases have been reported in which its use has given prompt relief in approximately 90 per cent of the patients.<sup>2</sup>Many of these patients have continued to use ergotamine tartrate over long periods of time. Possible development of ergotism from such prolonged use has been a source of some concern. It is my purpose in this study to analyze all the original reports concerning untoward sequelae of ergotamine tartrate therapy and to present some observations and deductions based on five years' experience with the drug in the treatment of migraine headache. <h3>LITERATURE</h3> Since the isolation of ergotamine tartrate by Stoll<sup>3</sup>in 1918, forty-two serious sequelae have been reported following its use.<sup>4</sup>Twenty-three have occurred in
Appraisal of Methysergide in Treatment of Vascular Headaches of Migraine Type
AbstractThe authors administered methysergide maleate to 421 patients who previously had been treated, without success, for recurrent headaches over periods as long as 55 yr. The drug was given in amounts ranging from 6 to 16 mg per day in divided doses. The treatment, essentially prophylactic, was continued for periods up to 29 mo. Side effects were frequent and adjustment of dosage was necessary. The data led to the conclusion that methysergide maleate has no value in treating the acute attack, but is effective in the prophylactic treatment of all forms of migraine headache.
Headache The Journal of Head and Face Pain · 2013 · 39 citations
Preventive Pharmacotherapy in Migraine
AbstractMigraine prevention can be instrumental in the effective management of the migraine patient but remains underused in treatment of this common, chronic, and often debilitating condition. The development of methysergide as the first migraine preventive agent not only laid the groundwork for our current thinking about migraine prevention, but also created a paradigm shift away from migraine as a psychological issue and toward migraine as a legitimate medical condition. This short review is intended to help the reader select patients appropriate for prevention and to initiate, monitor, and adjust preventive treatment. Goals in discussing preventive management are to facilitate provider familiarity with and confidence in this therapy leading to improved clinical outcomes and to a reduced burden of headache-related disability. Optimal therapeutic success is best achieved in the setting of a strong therapeutic alliance. Medication options for prevention are reviewed. Continued educational efforts directed at both patient and provider may be required to improve treatment utilization and reduce headache impact.
Headache The Journal of Head and Face Pain · 1985 · 20 citations
Effectiveness of Methysergide in Relation to Clinical Features of Migraine
AbstractSYNOPSIS Clinical data collected during a comparative trial of serotonin antagonists 1 was reanalysed to determine whether particular migrainous features were associated with a good response to methysergide. Patients with the fewest number of headache days per month and those with symptoms of cerebral disturbance before or during migraine had the best outcome.
The role of methysergide in migraine and cluster headache treatment worldwide – A survey in members of the International Headache Society
AbstractBackground Methysergide has been as an effective treatment for migraine and cluster headache for over 50 years but has recently been investigated by the European Medicines Agency due to safety concerns. Methods To assess the need for continuing availability of methysergide, the International Headache Society performed an electronic survey among their members. Results The survey revealed that 71.3% of all respondents had ever prescribed methysergide and 79.8% would prescribe it if it were to become available. Respondents used it more in cluster headache than migraine, and reserved it for use in refractory patients. Conclusion The vast majority of headache experts in this survey regarded methysergide a unique treatment option for specific populations for which there are no alternatives, with an urgent need to continue its availability. This position was supported by the International Headache Society.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, resolved on OpenAlex.
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