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dihydroergotamine mesylate (INP104 / I104 / Trudhesa)

✓ Approved

Impel Pharmaceuticals Inc · HTR1D · 小分子

什么是 dihydroergotamine mesylate？

dihydroergotamine mesylate 是一种小分子，由Impel Pharmaceuticals Inc研发。该药已获批，用于治疗相关适应症，给药途径：Inhaled、Intranasal。

药物档案

商品名INP104, I104, Trudhesa
公司Impel Pharmaceuticals Inc
药物类别小分子
分子靶点HTR1D
给药途径Inhaled, Intranasal
状态Approved
来源： ClinicalTrials.gov, Impel Pharmaceuticals Inc

作用机制

分子靶点

dihydroergotamine mesylate 作用于 1 个分子靶点：

HTR1D5-hydroxytryptamine receptor 1D (HTR1DA, HT1DA)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

dihydroergotamine mesylate 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Nervous system disordersMigraine✓ Approved

相关研究文献

PubMedMetabolites2026-07-27

Identification and Validation of a Lipid Metabolism-Related Gene Signature for Predicting Prognosis and Immunotherapy Response in Oral Squamous Cell Carcinoma.

Xie Yu Y, Chen Ziying Z, Chen Zhen Z, Yang Yiming Y

Background/Objectives: Lipid metabolism plays a critical role in tumor progression and immunotherapy efficacy in oral squamous cell carcinoma (OSCC). However, clinically applicable lipid metabolism-based models for predicting prognosis and immunotherapy response remain limited. This study aimed to develop and validate such a model in OSCC. Methods: Using transcriptomic data of OSCC from the TCGA database and a set of lipid metabolism-related genes (LMRGs), we constructed an LMRG-based risk score model via LASSO regression to predict patient survival. This model was subsequently validated using the independent GEO dataset GSE41613. Results: Patients in the high-risk group exhibited significantly poorer overall survival than those in the low-risk group (training cohort: p < 0.0001; validation cohort: p = 0.0086). We also developed a nomogram incorporating the risk score and clinical characteristics, and the risk score was identified as an independent prognostic factor for OSCC patients. Furthermore, the risk score was significantly associated with the tumor immune microenvironment; samples with a lower risk score showed elevated CD8+ T cell infiltration and a better response to immunotherapy. Additionally, the high-risk group exhibited an increased tumor mutation burden and resistance to most chemotherapeutic agents. Notably, several drugs (e.g., obatoclax mesylate) showed significant efficacy in the high-risk group, representing promising therapeutic candidates. Conclusions: This study reveals that the LMRG signature could serve as a valuable tool for prognosis assessment, risk stratification, and therapy guidance in OSCC.

PMID 42506409
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PubMedHospital pharmacy2026-07-25

Artificial Intelligence and Large Language Models as Decision-Support Tools in Hospital Compounding Pharmacy: A Proof-of-Concept Study.

Castellana Eleonora E, Chiappetta Maria Rachele MR

To evaluate the efficiency and reliability of a large language model (LLM) as a decision-support tool in hospital compounding pharmacy for pediatric extemporaneous preparations requiring assessment of drug crushability, regulatory compliance, and formulation feasibility. A proof-of-concept study compared a structured LLM-assisted workflow with the traditional manual information retrieval process in a hospital pharmacy setting. The LLM (Claude Sonnet 4.6) was configured with a standardized prompt to extract and consolidate data from multiple authoritative sources: the Friuli Venezia Giulia "Do Not Crush" list, the Italian Medicines Agency (AIFA) database for Summary of Product Characteristics (SmPC), AIFA Law 648/96 off-label use lists, and the Stabilis database for oral liquid formulation stability. Two representative drugs, propranolol hydrochloride and imatinib mesylate, were analyzed. For each drug, the model generated a structured output including crushability, regulatory information, off-label status, and extemporaneous formulation data. The same queries were manually performed by an experienced hospital pharmacist. Primary outcome was information retrieval time; secondary outcomes included completeness and accuracy. The LLM-assisted workflow reduced retrieval time to less than 2 minutes per drug (mean 1 minute 45 seconds), compared with a mean of 20 minutes (range 15-25 minutes) for the manual process, plus an additional 5 to 10 minutes for transcription. Output completeness was 100%, with all predefined fields correctly populated. The model accurately classified drug crushability and correctly identified Law 648/96 regulatory status. For propranolol, the system identified crushability, pediatric off-label authorization, and SyrSpend-based formulations with stability data of up to 146 days at room temperature. For imatinib, the model highlighted cytotoxic handling precautions, identified the absence of SyrSpend formulations, and retrieved alternative formulation stability data (30 days refrigerated). A properly configured LLM can function as an effective decision-support tool in hospital compounding pharmacy, improving efficiency while maintaining high standards of completeness, accuracy, and regulatory compliance. These preliminary results support further investigation into the integration of the LLM system into routine pediatric galenical preparation practice.

PMID 42500259
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PubMedScientific reports2026-07-21

Effect of targeted versus fixed dosing of nafamostat mesylate on filter life in patients undergoing continuous renal replacement therapy.

Rhee Harin H, Jung Kyung Sook KS, Ku Eun Young EY

Nafamostat mesylate (NM) is a commonly used anticoagulant in continuous kidney replacement therapy (CKRT) in Japan and South Korea. NM has been empirically infused at fixed doses (10-20 mg/h) without monitoring. In this single-center before-and-after study, we designed post-filter activated partial thromboplastin time (aPTT)-based targeted NM dosing protocol for CKRT and evaluated its efficacy and safety. The targeted NM dosing protocol involved titrating the NM dose (2.5-5 mg/h) to maintain the post-filter aPTT between 46 and 70 s. Efficacy was assessed by comparing filter lifespan before and after protocol implementation. Safety was evaluated based on changes in the incidence of bleeding complications, leukopenia, and hyperkalemia. Linear mixed-effects and Cox proportional hazards models were used, as appropriate. In total, 151 (before; 91, after; 60) patients received NM-CKRT anticoagulation (68.9% men, mean ages; 68.2 ± 14.2 years). Patient demographics and disease severity were similar before and after protocol implementation. During the intervention, 74.3% of filters reached the target aPTT levels. Compared with fixed dosing, post-filter aPTT-based targeted NM dosing extended the filter life by 4.5 (95% confidence interval; 1.5-7.5) h among filters that achieved the target aPTT levels, without compromising safety issues. Further validation across diverse centers is required.

PMID 42477433
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PubMedMediators of inflammation2026-07-21

MitoQ Ameliorates Diabetic Cardiomyopathy by Inhibiting the mtROS-TXNIP-NLRP3 Pathway.

Qian Shaohuan S, Leng Junjie J, Yao Zhuoya Z, Shi Chao C et al.

To determine whether mitoquinone mesylate (MitoQ) could treat diabetic cardiomyopathy (DCM) by inhibiting the mitochondrial reactive oxygen species (mtROS)/thioredoxin (TRX)-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) pathway. In vivo DCM models were established using a high-fat diet combined with streptozotocin injection in mice, whereas in vitro models were generated by exposing AC16 cardiomyocytes to high glucose. Immunohistochemistry (IHC) and western blotting were used to analyze the expression levels of TXNIP, NLRP3, Caspase-1, and other related proteins in cardiac tissue and cardiomyocytes stimulated with high glucose. mtROS fluorescence staining was used to analyze whether MitoQ could alleviate the generation of ROS in mitochondria in a high-glucose environment. Co-IP experiments were used to analyze whether high glucose stimulation promoted the interaction between TXNIP and NLRP3 and induced NLRP3 inflammasome activation. Diabetic mice exhibited increased oxidative stress, enhanced mtROS accumulation, activation of the TXNIP/NLRP3 inflammasome pathway, myocardial fibrosis, and impaired cardiac function. High-glucose stimulation in AC16 cells promoted dissociation of TXNIP from TRX, enhanced TXNIP-NLRP3 interaction, and increased expression of downstream pyroptosis-related proteins, including NT-gasdermin D (GSDMD), Caspase-1, and cleaved interleukin-1β (IL-1β). MitoQ treatment reduced mtROS production, restored mitochondrial membrane potential (MMP), inhibited TXNIP-NLRP3 interaction, and suppressed inflammasome activation both in vivo and in vitro. Moreover, TXNIP knockdown further enhanced the protective effects of MitoQ, confirming the critical role of the mtROS/TXNIP/NLRP3 axis. MitoQ attenuates diabetic myocardial injury by inhibiting mtROS accumulation and suppressing TXNIP/NLRP3 inflammasome activation. Targeting the mtROS/TXNIP/NLRP3 signaling pathway may represent a promising therapeutic strategy for DCM.

PMID 42479041
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PubMedJournal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology2026-07-21

Bioamine disruption leads to memory deficits in the whip spider, Phrynus marginemaculatus.

Ley Sidney T ST, Wolff Gabriella H GH, Casto Patrick P, Brown Nicholas A NA et al.

Amblypygi (whip spiders) are an order of arthropods (Subphylum: Chelicerata, Class: Arachnida) that navigate primarily by their keen olfactory abilities. Experiments in the laboratory reveal that the species Phrynus marginemaculatus forms both short and long-term memories for odors associated with access to a shelter. While bioamine function and location in the whip spider nervous system remain completely unexplored, comparative anatomy indicates that their olfactory memory may involve serotonin and dopamine signaling in brain regions involved in processing olfactory input. Preliminary immunohistochemistry detected serotonin and tyrosine hydroxylase immunoreactivity in mushroom body-associated calycal regions and antenniform primary olfactory glomeruli, supporting future work on monoaminergic modulation of olfactory circuits. Therefore, if serotonin or dopamine signaling involved in olfactory processing is pharmacologically disrupted, their performance in an associative olfactory learning task should be significantly impaired. Subjects were trained on an olfactory memory paradigm, subsequently injected with physiological saline, the serotonin receptor antagonist methiothepin mesylate (MET), or the dopamine receptor antagonist SCH-23390 (SCH), and tested for memory retention 24 h afterwards. Controls injected with saline demonstrated robust associative memory (serotonin antagonism control: n = 10, p = 0.006 against chance performance on the task, dopamine antagonism control: n = 10, p = 0.039), while treated groups displayed no such memory (MET: n = 10, p = 0.375, SCH: n = 10, p = 0.892). There was also a significant difference in performance between the treated and control groups on test day (serotonin antagonism groups: p = 0.048, dopamine antagonism groups: p = 0.016). Additionally, there were no significant differences in locomotor activity between treatment and control groups on test day (p > 0.05). Together, these results are consistent with serotonergic and dopaminergic signaling contributing to olfactory memory consolidation without grossly impairing locomotion in Phrynus marginemaculatus.

PMID 42479138
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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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