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dihydroergotamine mesylate (INP104 / I104 / Trudhesa)

✓ Approved

Impel Pharmaceuticals Inc · HTR1D · Small Molecule

What is dihydroergotamine mesylate?

dihydroergotamine mesylate is a small molecule developed by Impel Pharmaceuticals Inc. It is approved for therapeutic indications via inhaled or intranasal.

Drug Profile

Brand NamesINP104, I104, Trudhesa
CompanyImpel Pharmaceuticals Inc
Drug ClassSmall Molecule
Molecular TargetHTR1D
RouteInhaled, Intranasal
StatusApproved
Sources: ClinicalTrials.gov, Impel Pharmaceuticals Inc

Mechanism of Action

Molecular Targets

dihydroergotamine mesylate acts on 1 molecular target:

HTR1D5-hydroxytryptamine receptor 1D (HTR1DA, HT1DA)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

dihydroergotamine mesylate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Nervous system disordersMigraine✓ Approved

Related Research Articles

PubMedJournal of gastrointestinal cancer2026-07-17

Neoadjuvant Imatinib Therapy in Rectal Gastrointestinal Stromal Tumors: A Comprehensive Narrative Review of Tumor Downsizing, Sphincter Preservation, Transanal Surgical Platforms, Functional Outcomes, and Survival.

Raja Naga Praneeth NP, Kandagari Nagapavani N

Rectal gastrointestinal stromal tumors (GISTs) represent approximately 5-8.5% of all GISTs and pose unique surgical challenges due to the confined pelvic anatomy and proximity to the anal sphincter complex. Historically, radical surgery - including abdominoperineal resection (APR) or pelvic exenteration - was frequently required for complete tumor clearance, resulting in permanent colostomy and significant functional morbidity. The introduction of imatinib mesylate, a selective tyrosine kinase inhibitor (TKI) targeting KIT and PDGFRA, has fundamentally transformed the management of rectal GIST. Neoadjuvant imatinib therapy achieves significant tumor downsizing (25-46% reduction), reduces mitotic activity, and enables sphincter-preserving surgery in patients who would otherwise require radical resection. The concurrent evolution of transanal endoscopic platforms - including transanal endoscopic microsurgery (TEM), transanal minimally invasive surgery (TAMIS), and robotic TAMIS (R-TAMIS) - has further expanded the possibilities for organ preservation, achieving R0 resection rates of 89-100% with favorable functional outcomes and preserved fecal continence. Emerging evidence also suggests improvements in distant recurrence-free survival, disease-specific survival, and overall survival compared with upfront surgery. This comprehensive narrative review examines the rationale, efficacy, response assessment, surgical implications, the role of transanal surgical platforms, functional outcomes, quality of life, survival outcomes, and current guideline recommendations for neoadjuvant imatinib in rectal GIST.

PMID 42467291
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PubMedBMC nephrology2026-07-17

Comparative efficacy and safety of anticoagulation strategies in continuous renal replacement therapy: a real-world cohort study.

Ou Qing Q, He Dan D, Yan Wenjuan W, Shi Xiuying X et al.

The optimal anticoagulation strategy for continuous renal replacement therapy (CRRT) remains controversial. Real-world comparisons of contemporary agents-regional citrate anticoagulation (RCA), nafamostat mesylate (NM), and unfractionated heparin (UH)-are limited. In this single-center retrospective cohort study, we analyzed 420 CRRT sessions (from 197 unique patients) conducted in four intensive care unit (ICU) wards at an academic medical center in China between September 2025 and November 2025. The primary efficacy outcome was filter lifespan, with Restricted Mean Survival Time (RMST) analysis adopted as the primary method (due to violation of the proportional hazards assumption). Propensity score matching (PSM) and mixed-effects Cox models were used as sensitivity analyses, adjusting for patient, treatment, ward, and machine factors. Multiplicity adjustment (Holm-Bonferroni) was applied for pairwise comparisons. Among 420 sessions, RCA was the most frequently used approach (59.0%), followed by NM (21.2%), UH (12.6%), and no anticoagulation (4.0%). Median filter lifespan was longest with RCA (65.5 h, IQR 48.0-72.0) compared to NM (32.0 h, IQR 15.5-52.5), UH (40.0 h, IQR 26.0-72.0), and no anticoagulation (12.5 h, IQR 6.0-19.5; P < 0.001). RMST analysis confirmed that RCA was associated with significantly longer mean filter survival time compared to NM (difference 18.2 h, 95% CI 10.5-25.9; adjusted P < 0.001) and UH (difference 14.6 h, 95% CI 5.8-23.4; adjusted P = 0.046). The NM vs. UH comparison showed no significant difference (difference - 3.6 h, 95% CI -12.1 to 4.9; adjusted P = 0.52). After PSM, results remained consistent. Major bleeding events were rare (n = 9, 2.1%), but the small number of events precludes meaningful between-group safety comparison. However, 20.9% of RCA sessions failed to achieve the protocol-specified post-filter ionized calcium target, reflecting a metabolic calcium monitoring challenge unique to citrate anticoagulation. Twenty-eight-day mortality (patient-level analysis, n = 197) did not differ significantly across groups after adjustment (overall 36.5%, 72/197). In this retrospective data analysis of real-world practice, RCA provided superior filter lifespan compared to NM and UH for CRRT, while NM showed intermediate efficacy. Although major bleeding events were uncommon, the small number of events precludes definitive safety conclusions. Vigilant monitoring remains necessary regardless of the agent employed. The choice of anticoagulation should balance filter efficacy, bleeding risk, metabolic monitoring capabilities, and institutional resources.

PMID 42464171
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PubMedFrontiers in pharmacology2026-07-16

Sodium selenite attenuates sepsis-induced cardiac inflammation and oxidative injury by regulating TXN2/TXNIP/NLRP3 signaling and ferroptosis.

Zhang Lei L, Zhu Dandan D, Yu Jian J

Septic cardiomyopathy is cardiac dysfunction caused by sepsis and is a common consequence of sepsis. Clinical studies have found patients with sepsis syndrome commonly have low serum selenium (Se) levels, and Se supplementation at doses higher than the daily requirement may reduce mortality; however, the underlying mechanism remains unclear. We found that downregulation of thioredoxin-2 (TXN2)-induced mitochondrial reactive oxygen species (mtROS), which increased inflammatory and oxidative injury in cardiomyocytes, might be a major contributor to septic cardiomyopathy. Mitoquinone mesylate (MitoQ), an antioxidant specifically targeted to mitochondria, increased TXN2 expression and decreased mtROS, thioredoxin-interacting protein (TXNIP, a negative regulator of TXN), nucleotide-binding oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome activation, and ferroptosis. The results suggest that the TXN2-ferroptosis-NLRP3 pathway may represent a therapeutic target for sepsis-induced cardiac injury. In addition, we found that Se supplementation improved cardiac function and relieved mtROS accumulation and ferroptosis in sepsis-associated cardiac injury by regulating TXN2 and TXNIP/NLRP3 expression.

PMID 42460027
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PubMedPaediatric drugs2026-07-13

Safety and Effectiveness of Pain Medications for Migraine Management During Pregnancy and Lactation.

Smirnoff Liza L, Mancera Nicolas Garzon NG, Hyppolite Tayina T, Lozano Daniela D et al.

The management of migraine during pregnancy and lactation poses a major challenge owing to the paucity of safety data. While very little safety data are available for new targeted migraine therapies such as calcitonin gene receptor protein (CGRP) blocking medications, including the CGRP monoclonal antibodies and gepants, well-established migraine therapies such as topiramate, valproate, and dihydroergotamine have known risk for teratogenicity. Likewise, the safety evidence for commonly used therapies for migraine in pregnancy such as propranolol and verapamil is of low quality, and the level of evidence for efficacy of verapamil is limited. Meanwhile women experience migraine at the highest rates during their reproductive years necessitating an effective and balanced approach that considers maternal and fetal risk as well as optimal benefit to the patient to ensure adequate and appropriate treatment during pregnancy and lactation. The purpose of this review is to provide an overview of the available data on the safety of available and efficacious medications in the management of migraine during pregnancy and lactation. Based on more recent studies, there is increased evidence for use of more specific and efficacious medications for migraine, such as onabotulinumtoxinA, local nerve blocks with lidocaine, and triptans during pregnancy and lactation.

PMID 42440212
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PubMedMolecular diversity2026-07-09

Dihydroergotamine alleviates circadian rhythm disorders through predicted interaction with to CRY1.

Cai Linhui L, Sun Yixin Y, Wang Shuai S, You Qianqian Q et al.

Circadian rhythm disorders (CRDs) significantly affect human health, yet therapeutic options remain limited. This study employed a multi-scale virtual screening approach to identify novel drug candidates from FDA-approved small molecules for the treatment of CRDs. We screened 1429 FDA-approved small molecules against five key circadian rhythm-related proteins using molecular docking techniques. The screening process incorporated the TOPSIS algorithm for multi-criteria decision analysis and a machine learning-based assessment of gut microbiota impact. Our computational analysis identified dihydroergotamine (DHE) as the top-ranking candidate, with predicted favorable binding profiles and minimal predicted adverse effects on gut microbiota. Molecular dynamics simulations supported the stability of the modeled DHE-6KX4 complex, indicating sustained interactions in silico over a 100 ns simulation time. Moreover, DHE significantly alleviated physiological and behavioral abnormalities induced by sleep deprivation, including weight loss, recognition memory deficits, and disruption of sleep architecture. Mechanistically, DHE promoted the accumulation of the PER1-CRY1 complex in the nucleus, which subsequently suppressed CLOCK expression, leading to the restoration of normal circadian rhythm function. This integrated computational-experimental approach provides a robust framework for drug repurposing in circadian medicine, establishing DHE as a promising repurposing candidate for CRDs. Notably, the direct interaction between DHE and CRY1 remains a computational prediction that requires further experimental validation.

PMID 42423922
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PubMedAmerican journal of physiology. Renal physiology2026-07-09

Eight Weeks of MitoQ Supplementation Does Not Alter Kidney Function or Urinary Kidney Injury Biomarkers in Middle-Aged and Older Adults.

Stute Nina L NL, Muma Jake P JP, Hutchison Zach J ZJ, Culver Meral N MN et al.

Introduction: Several human trials have used the mitochondrial antioxidant mitoquinol mesylate (MitoQ). There are no apparent negative consequences on the kidneys following an acute high dose of MitoQ in young adults, however it remains unclear whether chronic MitoQ influences kidney function. Therefore, we examined whether eight weeks MitoQ supplementation (20mg/day) impacts kidney function and kidney injury biomarkers using a randomized, placebo-controlled, crossover study in middle-aged and older adults (n=30, 8 males/22 females, 57±8 years). Methods: Participants completed four visits (pre- and post-placebo; pre- and post-MitoQ) where we collected serum samples (creatinine and cystatin c) and 24-hr urine samples to assess general kidney function (estimated glomerular filtration rate [eGFR] and creatinine clearance), and kidney injury markers (neutrophil gelatinase-associated lipocalin; NGAL, kidney injury molecule-1; KIM-1, nephrin, tissue inhibitor of metalloproteinase-2; TIMP-2, and insulin-like growth factor binding protein-7; IGFBP7). We used mixed-effects models to examine time, condition, and interaction effects. Results: We observed no alterations in glomerular filtration measures (ps ≥ 0.309), or kidney injury markers when indexed to flow rate, osmolality, or creatinine (ps ≥ 0.198). For example, TIMP-2 × IGFBP7 was not different between groups (pre placebo: 114 ± 162, post placebo: 138 ± 161; pre MitoQ: 162 ± 238, post MitoQ: 127 ± 137 ng2/min; interaction p = 0.754). Conclusion: Eight weeks of MitoQ supplementation doesn't appear to benefit or harm kidney function or kidney injury markers in middle-aged and older adults.

PMID 42420763
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