dihydroergotamine mesylate injection / Generic mfg. - LARVOL DELTA

First in human study to evaluate pharmacokinetics, safety and tolerability of a novel in-development dihydroergotamine mesylate (DHE) inhalation powder delivered via a multidose dry powder inhaler (DPI) (AHS 2025) - "Background: Migraine remains a serious cause of disability with significant financial and socioeconomic burden and 37.4%–74.1% still report dissatisfaction with their current acute treatment.3,4 Reasons for this include narrow treatment window, GI dysmotility leading to poor oral absorption, slow speed of onset, high pain recurrence and poor tolerability.3,4 Dihydroergotamine (DHE), supported by over 70 years of clinical practice data, is established as safe and effective in acute treatment of migraine.1 Intravenous (IV) DHE provides fast onset, sustained efficacy and minimal risk of medication-overuse headache.1,7 However, its use is limited by poor tolerability (such as nausea and vomiting) and in-hospital administration.1,7 Two approved DHE intranasal (IN) formulations (Migranal® and Trudhesa®) address some of the limitations of the IV DHE.5–7 However, Migranal®, nasal spray delivering to lower nasal space, has limitations of low bioavailability,..."

Clinical • P1 data • PK/PD data • CNS Disorders • Migraine • Pain

Aprepitant for primary nausea control for pediatric patients during repetitive dihydroergotamine infusions (AHS 2025) - "The data suggests that patients who received aprepitant were more likely to receive additional anti-emetics during DHE treatments. Given that this study is a retrospective cohort study at a single institution, more studies are necessary in order to determine the external validity of this study. It is important to control nausea in patients receiving DHE so they are able to complete treatment for migraine and there appears to be a trend of an increased number of patients who completed the DHE protocol when administered with aprepitant."

Clinical • CNS Disorders • Migraine • Pain

Disparities in inpatient dihydroergotamine administration in pediatric patients with headache at the Children's Hospital of Philadelphia (AHS 2025) - "Non-Hispanic and White patients had higher odds of receiving DHE compared to non-Hispanic patients and those of other races who were diagnosed with migraine. For certain minoritized populations, sample sizes were likely not large enough to obtain statistically significant differences. We must conduct further investigation to understand potential reasons for such disparities which are likely related to inequity in rates of admission for migraine and rates of IV medication both of which have been demonstrated in our previous work."

Clinical • CNS Disorders • Migraine • Pain

The long-term impact of COVID-19 on admissions for migraine with DHE: A descriptive analysis (AHS 2025) - "One Sentence Summary: A significant decline in admissions for the treatment of migraine with dihydroergotamine (DHE) was observed during the COVID-19 pandemic and remained markedly lower than pre-pandemic levels in subsequent years... A significant and sustained decline in admissions for treatment of migraine with DHE was observed at the onset, during and after the COVID-19 pandemic. While this trend may reflect broader changes in healthcare delivery and patient care-seeking behaviors triggered at least in-part by the pandemic, further research is needed to determine the specific factors contributing to this decline, including potential shifts in prescribing patterns, patient preferences, and healthcare accessibility. FIGURE 1."

CNS Disorders • Migraine • Pain

What to Do When Prior Acute Migraine Treatments Fail: Underlying Mechanisms and Treatment Approaches (AHS 2025) - "Current therapeutic options for acute migraine treatment include new drug classes (gepants, ditans), as well as novel delivery options of established drug classes (dihydroergotamine, triptans, NSAIDs). A newly approved therapeutic option is a multi-mechanistic approach that targets several pathophysiologic mechanisms through a novel formulation of meloxicam and rizatriptan combined in the same tablet. The symposium will highlight the pathophysiologic processes and multi-mechanistic approaches for acute treatment of migraine, including therapies to consider when previous acute treatments fail or when response is inadequate.Educational ObjectivesUpon completion of this activity, participants should be able to:• Identify central, peripheral, neuronal, and vascular pathophysiologic mechanisms involved in acute migraine pain• Explain the scientific rationale for multi-mechanistic targeting of pathophysiologic mechanisms of acute migraine in patients with inadequate response..."

CNS Disorders • Migraine • Pain

Peripheral blood immune landscape and NXPE3 as a novel biomarker for hypertensive intracerebral hemorrhage risk prediction and targeted therapy. (PubMed, Imeta) - "Molecular docking and simulation results demonstrated that NXPE3 is a potential therapeutic target, and dihydroergotamine (DHE) exhibits a strong binding affinity to NXPE3. In vivo experiments indicated that DHE can reduce the incidence of spontaneous ICH and modulate the immune-inflammatory response. These results support DHE targeting NXPE3 as a potential therapeutic strategy for hypertension-related ICH."

Biomarker • Journal • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Hypertension • Inflammation

Myocardial Infarction With Nonobstructive Coronary Arteries: A Significant Adverse Effect of Dihydroergotamine. (PubMed, Cureus) - "Despite long-term use without prior adverse effects, our patient developed MINOCA after receiving DHE to treat migraine attacks, highlighting the unpredictable nature of DHE's vasoconstrictive effects and underscoring the need for heightened clinical vigilance, especially in patients with underlying cardiovascular risk factors. Given the diagnostic and prognostic ambiguity surrounding MINOCA, this case contributes to the growing body of literature advocating for individualized risk assessment and cautious DHE administration."

Adverse events • Journal • Acute Coronary Syndrome • Cardiovascular • CNS Disorders • Inflammation • Migraine • Myocardial Infarction • Pain

In silico drug repurposing for potential HPV-induced skin wart treatment - A comparative transcriptome analysis. (PubMed, J Genet Eng Biotechnol) - "Dihydroergotamine can be repurposed as a potential drug in the treatment of skin warts by targeting Integrin Alpha-X protein."

Journal • Cervical Cancer • Dermatology • Human Papillomavirus Infection • Infectious Disease • Oncology • Solid Tumor • ITGAX

A fixed-dose combination of meloxicam and rizatriptan (Symbravo) for migraine. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine • Pain

Tolerability of repetitive dihydroergotamine infusions paired with an adjustment in preventive treatment strategy in chronic headache disorders in children and youth. (PubMed, J Headache Pain) - "Repetitive DHE infusions followed by preventive treatment adjustment was well tolerated and significantly reduced headache frequency, baseline intensity, number of severe days and/or acute medication usage in children and youth with refractory headache disorders."

Journal • CNS Disorders • Migraine • Pain • Pediatrics

Polypharmacy and Trends in Pharmacologic Management in Patients with Refractory Spontaneous Intracranial Hypotension (SIH) (AAN 2025) - "Prescription medications were categorized by class: triptans, dihydroergotamines, anti-CGRP monoclonal antibodies, CGRP antagonists, NSAIDs, antidepressants, antihypertensives, and anticonvulsants...Medication trials for refractory SIH may contribute to polypharmacy in a subset of patients. Further investigation into the impact of polypharmacy in SIH patients is warranted."

Clinical • CNS Disorders • Hypotension • Migraine • Pain

Identification of potential diagnostic targets and therapeutic strategies for anoikis-related biomarkers in lung squamous cell carcinoma using machine learning and computational virtual screening. (PubMed, Front Pharmacol) - "Dihydroergotamine exhibited significant anti-LUSC activity and holds promise as a potential therapeutic agent. CSNK2A1 emerged as a robust candidate for early diagnosis and a therapeutic target in LUSC."

Biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Exploring bacterial key genes and therapeutic agents for breast cancer among the Ghanaian female population: Insights from In Silico analyses. (PubMed, PLoS One) - "Subsequently, the bKG-guided top ranked 10 drug molecules Digitoxin, Digoxin, Ledipasvir, Suramin, Ergotamine, Venetoclax, Nilotinib, Conivaptan, Dihydroergotamine, and Elbasvir were identified using molecular docking analysis. The stability of top-ranked three drug-target complexes (Digitoxin-pykA, Digoxin-mdh, and Ledipasvir-pgi) were confirmed through the molecular dynamics simulation studies. Therefore, these findings might be useful resources to the wet-lab researchers for further experimental validation on bacterial therapies against BC."

Journal • Breast Cancer • Infectious Disease • Oncology • Solid Tumor

Relationship of dihydroergotamine pharmacokinetics, clinical efficacy, and nausea-A narrative review. (PubMed, Headache) - "The maximum concentration and AUC over the first 30 min following DHE administration were associated with increasing rates of 2hPR and a Cmax below ~2500 pg/mL was associated with low incidences of nausea. We suggest that this may be an optimal profile for a DHE delivery form. Further research to test this hypothesis is warranted."

Journal • PK/PD data • Review • CNS Disorders • Migraine • Pain

Facial Nerve Palsy, Left Upper Extremity Weakness, and the Absence of Papilledema in an 8-year-old Child with Idiopathic Intracranial Hypertension: A Case Report (ANA 2024) - "The patient's occipital pain was minimally responsive to over-the-counter anti-inflammatories, migraine cocktails, and abortive migraine treatment with dihydroergotamine...She was prescribed maintenance acetazolamide and instructed to follow outpatient with pediatric neurology for management of her newly diagnosed IIH. IIH cannot definitively be excluded in the absence of papilledema or in the presence of atypical features, such as an isolated facial nerve palsy or polyradiculopathy. A high index of suspicion for IIH should remain, particularly in children, as it is a sight-threatening condition if left untreated."

Case report • Clinical • CNS Disorders • Migraine • Pain

Recent Development of Zolmitriptan Formulation in Migraine Therapy: Production, Metabolism and Pharmaceutical Aspects. (PubMed, CNS Neurol Disord Drug Targets) - "At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists...The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine...Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features."

Journal • CNS Disorders • Migraine • Pain

Citrullination modulation stabilizes HIF-1α to promote tumour progression. (PubMed, Nat Commun) - "Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Von Hippel-Lindau Syndrome • HIF1A • PADI4

Molecular Docking-Based Virtual Screening of FDA-Approved Drugs Using Trypanothione Reductase Identified New Trypanocidal Agents. (PubMed, Molecules) - "Digoxin, alendronate, flucytosine, and dihydroergotamine showed better trypanocidal activity than the reference drugs benznidazole and nifurtimox in the in vitro evaluation against the trypomastigotes form. Further, these FDA-approved drugs were able to reduce 20-50% parasitemia in a short time in an in vivo model, although with less efficiency than benznidazole. Therefore, the results suggest a combined therapy of repurposed and canonical drugs against T. cruzi infection."

FDA event • Journal • Preclinical • Infectious Disease

Dihydroergotamine and Bromocriptine: Potential Drugs for the Treatment of Major Depressive Disorder and Alzheimer's Disease Comorbidity. (PubMed, Mol Neurobiol) - "The exact mechanisms of the two drugs in treating AD and MDD, as well as their comorbidity, are still unclear, and further exploration is needed to evaluate their roles and mechanisms, both in vitro and in vivo. This study revealed that dihydroergotamine and bromocriptine may be the potential drug candidates for the treatment of the comorbidity of AD and MDD, and the therapeutic effects may be achieved by inhibiting the accumulation and aggregation of Aβ42 and tau protein and regulating the expression of disease-related genes in the brain."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Aβ42

Identifying potential drug targets in the kinomes of two monogenean species. (PubMed, Helminthologia) - "Molecular docking analysis indicated that dihydroergotamine, ergotamine, and lomitapide have the highest affinity for the kinases BRSK and MEKK1. These well-known drugs could be evaluated in future studies for potential repurposing as anti-monogenean agents. The present study contributes valuable data for the development of new antiparasitic candidates for finfish aquaculture."

Journal • MAP2K1 • MAP3K1

Real-world approaches to outpatient treatment of status migrainosus: A survey study. (PubMed, Headache) - "Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management."

Journal • Real-world • Real-world evidence • CNS Disorders • Infectious Disease • Migraine • Novel Coronavirus Disease • Pain

Onset, characteristics, treatments, and burden of New Daily Persistent Headache: Initial data from the NDPH Patient Experience Survey (AHS 2024) - "The three most effective acute treatments reported were hydrocodone, dihydroergotamine injections, and tramadol while the three most effective preventive treatments were eptinezumab, atogepant, and rimegepant: the three acute and three preventive treatments were found to be somewhat, very, or completely effective in 46–56% of respondents. NDPH can occur at any age, with some epidemiologic features and burden similar to chronic migraine. Rates of opioid use were high, supporting a large unmet treatment burden, and anti-CGRP treatments appear to show the most effectiveness in preventive management."

Clinical • CNS Disorders • Depression • Migraine • Pain • Psychiatry • Sleep Disorder

Treatment of pediatric migraine in the emergency department: The importance of timely medication administration and intravenous dihydroergotamine (AHS 2024) - "Pediatric headaches are a common reason for presentation to the ED. Migraine cocktails are an effective treatment option for ongoing pediatric headaches with 83% of all encounters discharging after migraine cocktails ± valproic acid. Amongst patients that are refractory to migraine cocktails, an additional 20% are able to discharge after receiving IV DHE."

Clinical • CNS Disorders • Migraine • Pain

Zavegepant for the acute treatment of cluster headache: A case series (AHS 2024) - "Currently, triptans, dihydroergotamine (DHE), and oxygen therapy are the mainstays of treatment...Calcitonin gene-related peptide (CGRP) has a significant role in cluster headache, as demonstrated by the effectiveness of galcanezumab, a humanized monoclonal antibody against CGRP, as well as various foundational research... CH is a primary headache disorder which has been shown to have limited therapeutic options, especially in patients with cardiovascular/cerebrovascular risk factors. This case series aimed to suggest the efficacy of zavegepant as a possible potent therapeutic agent for the treatment of an acute CH attack. In the five cases demonstrated in this study, zavegepant provided significant and rapid onset relief of symptoms of attacks of CH."

Clinical • CNS Disorders • Migraine • Pain

Repurposing FDA-approved compounds to target JAK2 for colon cancer treatment. (PubMed, Discov Oncol) - "Our results indicated that ergotamine, entrectinib, exatecan, dihydroergotamine, and paritaprevir can be used as alternative drugs for colon cancer. The long-term inhibitory effect of the ergotamine led to a decrease in colony size, and the toxicity properties were studied using hemolysis assay. Our study shows the potential of targeting JAK2 as a novel approach to colon cancer treatment, and demonstrate that ergotamine as a promising effects as an anti-cancer drug."

FDA event • Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Oncology • Solid Tumor • IL6