- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Drug Development. (Pubmed Central) - Jan 12, 2025
This was associated with its potent inhibition of inflammation, pyroptosis, and associated synapse protein loss. IDNs emerge as a promising therapeutic intervention for both depression and dementia, particularly in AD.
- |||||||||| lithium carbonate ER / Generic mfg., Ryanodex (dantrolene) / Eagle Pharma
Journal: Drug Development. (Pubmed Central) - Jan 12, 2025
Intranasal LiCl in RFV ameliorates memory loss and depressive behavior in 5XFAD mice without side effects or organ toxicity, with chronic use. Intranasal LiCl in RFV effectively inhibited, oxidative stress, inflammation and pyroptosis in aged 5XFAD brains.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Trial completion date, Trial primary completion date: A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias. (clinicaltrials.gov) - Dec 18, 2024
P2/3, N=84, Active, not recruiting,
Intranasal LiCl in RFV effectively inhibited, oxidative stress, inflammation and pyroptosis in aged 5XFAD brains. Trial completion date: Nov 2024 --> Jan 2026 | Trial primary completion date: Nov 2024 --> Mar 2025
- |||||||||| lithium carbonate ER / Generic mfg.
Preclinical, Journal: Intranasal Lithium Chloride Nanoparticles Inhibit Inflammatory Pyroptosis in Brains and Ameliorate Memory Loss and Depression Behavior in 5xFAD mice. (Pubmed Central) - Sep 30, 2024
This study compares the changes in lithium concentrations in the brain and blood following the administration of intranasal or oral lithium chloride (LiCl) dissolved in either Ryanodex Formulation Vehicle (RFV) or water, as well as the therapeutic effectiveness and side effects of intranasal versus oral lithium chloride (LiCl) in RFV, and their mechanisms for inhibiting inflammation and pyroptosis in 5xFAD Alzheimer's Disease (AD) mice brains...This lithium mediated neuroprotection was associated with its potent effects on the inhibition of InsP3R-1 Ca 2+ channel receptor increase, ameliorating pathological inflammation and activation of the pyroptosis pathway, and the associated loss of synapse proteins. Intranasal LiCl in RFV could become an effective and potent inhibitor of pathological inflammation/pyroptosis in the CNS and treat both dementia and depression with no or minimal side effects/organ toxicity, particular in AD.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Dysregulated RyR-Ca2+signaling drives mitochondrial dysfunction in AD neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2398;
Additionally, increased susceptibility to apoptosis was observed in AD HiNs with increased caspase 3 activity and an increased pool of readily releasable cytochrome c.Our data demonstrate that dysregulated RyR-Ca2+ signaling can act as an upstream mechanism of mitochondrial dysfunction. The complete or partial rescuing of mitochondrial functions through pharmacological interventions emphasizes the importance of dysfunctional RyR-Ca2+ signaling as a driving factor for mitochondrial dysfunction and provides a potential therapeutic target for combating cellular dysfunction in early AD.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Trial completion date, Trial primary completion date: A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias. (clinicaltrials.gov) - Jul 10, 2024
P2/3, N=84, Active, not recruiting,
The complete or partial rescuing of mitochondrial functions through pharmacological interventions emphasizes the importance of dysfunctional RyR-Ca2+ signaling as a driving factor for mitochondrial dysfunction and provides a potential therapeutic target for combating cellular dysfunction in early AD. Trial completion date: Jun 2024 --> Nov 2024 | Trial primary completion date: Jun 2024 --> Nov 2024
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Preclinical, Journal: Effects of Intranasal Dantrolene Nanoparticles on Brain Concentration and Behavior in PS19 Tau Transgenic Mice. (Pubmed Central) - Mar 25, 2024
The behavioral assays showed no significant changes in cognition, olfaction, or motor function in the PS19 mice compared to controls after chronic treatment with intranasal ERFR, even with acrolein. Our studies suggest the intranasal administration of ERFR has higher concentrations in the brain than the blood in aged mice and has no serious systemic side effects with chronic use in PS19 mice.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Enrollment closed: A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias. (clinicaltrials.gov) - Feb 15, 2024
P2/3, N=84, Active, not recruiting,
Our studies suggest the intranasal administration of ERFR has higher concentrations in the brain than the blood in aged mice and has no serious systemic side effects with chronic use in PS19 mice. Recruiting --> Active, not recruiting
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Elevated ER-Ca2+signaling in human AD neurons drives disruptions in mitochondrial functions (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_4647;
In neurons from AD patients, resting mitochondrial Ca2+ levels, membrane potential, and superoxide production were significantly higher than in non-AD neurons and was normalized by the RyR negative allosteric modulator, Ryanodex (10uM)...The data demonstrate that elevated RyR-Ca2+ signaling elicits a maladaptive response within the mitochondria that links with AD features such as impaired cellular metabolism and increased free radical production. Thus, identifying the pathogenic cascades within the mitochondria that result from elevated ER-Ca2+ release is essential for elucidating cellular disease mechanisms in early AD.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
A cascade of intracellular organelle defects drives cellular pathophysiology in Alzheimer (WCC 207A) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_1380;
These results highlight that aberrant ER Ca2+ signaling disrupts a series of key organelle interactions that collectively drive a neuronal AD phenotype, and point to shared pathogenic mechanisms between AD and DS. Furthermore, pharmacological suppression of RyR-Ca2+ release rescues organelle function, revealing a target for therapeutic intervention that has demonstrated effects in clinically-relevant assays.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Trial primary completion date: A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias. (clinicaltrials.gov) - Jul 28, 2023
P2/3, N=84, Recruiting,
Furthermore, pharmacological suppression of RyR-Ca2+ release rescues organelle function, revealing a target for therapeutic intervention that has demonstrated effects in clinically-relevant assays. Trial primary completion date: Jun 2023 --> Jun 2024
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
PROTEIN MISHANDLING AND MITOCHONDRIAL PATHOPHYSIOLOGY DRIVEN BY CALCIUM DYSHOMEOSTASIS IN ANIMAL AND HUMAN MODELS OF AD (ONSITE - HALL G4) - Dec 23, 2022 - Abstract #ADPD2023ADPD_386;
Normalizing AD-associated aberrant RyR Ca2+ signaling with dantrolene (Ryanodex) restored physiological functioning of these critical organelles. Conclusions These results highlight that aberrant upstream Ca2+ signaling disrupts lysosomal acidification, autophagic processes and mitochondrial functions, and suppressing RyR-Ca2+ release offers a therapeutic intervention that has demonstrated effects in clinically-relevant assays.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Protein mishandling and impaired lysosomal proteolysis generated through calcium dysregulation in Alzheimer's disease. (Pubmed Central) - Nov 29, 2022
Normalizing AD-associated aberrant RyR-Ca signaling with the negative allosteric modulator, dantrolene (Ryanodex), restored vATPase levels, lysosomal acidification and proteolytic activity, and autophagic clearance of intracellular protein aggregates in AD neurons...Importantly, this is demonstrated in animal models of AD, and in human iPSC-derived neurons from AD patients. Furthermore, pharmacological suppression of RyR-Ca release rescued proteolytic function, revealing a target for therapeutic intervention that has demonstrated effects in clinically-relevant assays.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Effects of intranasal dantrolene on cognitive function in P301S (line PS19) tau pathology mice (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_1650;
Grant Support: National Institute on Aging Grant (R01AG061447), Eagle UPENN collaborative fund #578808This study investigates whether intranasal administration of Eagle Research Formulation of Ryanodex (ERFR), a dantrolene formulation, is neuroprotective in tau pathology mice (P301S, Line PS19)...Our results suggest that PS19 mice may not be a reliable AD animal model to test therapeutic efficacy of new or repurposed dantrolene drug products. In the future, intranasal dantrolene drug products will be tested in a suitable animal model with significant sporadic AD (SAD) risk factors.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Simulation Training: A Multidisciplinary Approach (Hall C) - Aug 15, 2022 - Abstract #ASA2022ASA_3481;
We conducted several simulations to prevent OR fires, introduce Ryanodex, and treat local anesthetic toxicity...Through our interdisciplinary sessions, we were able to foster a sense of trust, openness, and excitement among all members. Our debriefing sessions allowed for better communication and teamwork.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Lysosome-autophagosome defects mediate proteinopathy in Alzheimer's disease pathogenesis (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_2734;
Protein aggregates, such as β-amyloid and hyperphosphorylated tau, were increased in iNs with V-ATPase inhibition (bafilomycin 125 nM), which was resolved with Ryanodex treatment. Prior to overt histopathology or cognitive deficits, abnormal RyR-mediated Ca 2+ release disrupts lysosomal function leading to altered autophagic-mediated protein clearance that contributes to AD proteinopathy.; Grant Support: NIH R56 AG055497
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
An Unusual Case Of Malignant Hyperthermia (Exhibit Hall) - Sep 25, 2021 - Abstract #ASA2021ASA_4663;
Following diagnosis, the patient was treated with Ryanodex 2.5 mg/kg x 2 and other measures, resulting in prompt and dramatic resolution of his hypercarbia (ETCO2 127 to 44) and other vital signs. This case highlights the need for continuous vigilance, early and accurate diagnosis, and expeditious treatment of this rare and potentially fatal anesthesia complication.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Optimizing Malignant Hyperthermia Response (Exhibit Hall) - Sep 25, 2021 - Abstract #ASA2021ASA_3841;
The next pediatric NORA MH case saw dantrolene administration time reduced by 94% and ICU stay reduced by 40%. The MH Tackle Box includes major components of the guideline-based MH Cart and enables timely resuscitation in NORA settings.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Preclinical, Journal: Intranasal Dantrolene as a Disease-Modifying Drug in Alzheimer 5XFAD Mice. (Pubmed Central) - Jun 4, 2021
Postoperatively his CPK was elevated, peaking at 7117, but all other metabolic derangements resolved by POD #1. The long-term intranasal administration of dantrolene had therapeutic effects on memory compared to the subcutaneous approach even started after onset of AD symptoms, suggesting use as a disease-modifying drug, without significant effects on amyloid plaques, side effects, or mortality.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Enrollment change, Trial termination: Efficacy and Safety Study of Ryanodex as Adjuvant Treatment in Subjects With Psychostimulant Drug-Induced Toxicity (PDIT) (clinicaltrials.gov) - Mar 30, 2021
P2, N=2, Terminated,
The long-term intranasal administration of dantrolene had therapeutic effects on memory compared to the subcutaneous approach even started after onset of AD symptoms, suggesting use as a disease-modifying drug, without significant effects on amyloid plaques, side effects, or mortality. N=100 --> 2 | Active, not recruiting --> Terminated; Limited enrollment
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma, Comfyde (carisbamate) / J&J, SK Bio
Review, Journal: Novel therapeutics for treating organophosphate-induced status epilepticus co-morbidities, based on changes in calcium homeostasis. (Pubmed Central) - Dec 19, 2020
These Ca elevations had their origin in Ca release from the intracellular stores such that blockade with antagonists like dantrolene, carisbamate, and levetiracetam lowered OP-SE mediated Ca plateau and afforded significant neuroprotection. Since the Ca plateau lasts for a prolonged period, our studies suggest that blocking it after the control of SE may represent a unique target for development of novel countermeasures to prevent long term Ca mediated OP-SE neuropsychiatric comorbidities such as depression, anxiety, and acquired epilepsy (AE).
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Clinical, Review, Journal: Neuroleptic malignant syndrome in patients with cancer: a systematic review. (Pubmed Central) - Dec 16, 2020
Although NMS intrinsically has a low incidence and high mortality, only few reports were available, with most patients surviving after early detection and appropriate treatment. Healthcare providers should consider NMS development while prescribing antipsychotics to ensure prompt recognition of the condition and rapid treatment for preventing unnecessary deaths.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Loss of tumor susceptibility gene 101 (TSG101) perturbs endoplasmic reticulum structure and function. (Pubmed Central) - Dec 16, 2020
Inhibiting Ca release from the ER by blocking ryanodine receptors (RYRs) with Dantrolene partially rescues the ER stress phenotypes...SUMMARY STATEMENT: We show that tumor susceptibility gene (TSG) 101 regulates endoplasmic reticulum (ER) stress and its membrane remodelling. Loss of TSG101 perturbs structure, mobility and function of the ER as a consequence of actin destabilization.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells. (Pubmed Central) - Dec 16, 2020
In addition, dantrolene treatment, which inhibits Ca release through ryanodine receptor channels, also inhibited C. lanceolata- or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway...C. lanceolata or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Clinical, Journal: Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis? (Pubmed Central) - Dec 15, 2020
Additionally, dantrolene has also been shown to inhibit multiple cell or organ damage induced by hypoxia/ischemia, mitochondria damage, oxidative stresses, inflammation, impairment of autophagy and apoptosis, etc., which are often the causes of severity and mortality of COVID-19 patients. We have repurposed that dantrolene has a high potential at treating COVID-19 patients and reducing its morbidity and mortality.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Rhabdomyolysis during Perioperative Period after Cardiac Surgery (Pubmed Central) - Dec 15, 2020
It remained unclear which drug triggered rhabdomyolysis. When MH is suspected, we should consider the use of the clinical grading scale to predict its susceptibility and start dantrolene sodium hydrate infusion.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Review, Journal: Malignant Hyperthermia Update. (Pubmed Central) - Nov 19, 2020
Genetic testing is also available. MH-susceptible individuals should be clearly identified for safe administration of future anesthetics.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma, Silverzine Tulle (Silver Sulfadiazine) / MinaPharm
Journal: Mechanochemical Preparation of Active Pharmaceutical Ingredients Monitored by In Situ Raman Spectroscopy. (Pubmed Central) - Nov 18, 2020
Moreover, the kinetic features of the mechanochemical process were examined by a mathematical model allowing to describe the chemical changes under mechanical stress. This approach is promising both to broaden the scope of Raman in situ investigations that would otherwise be impossible and for process optimization at any scale.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Preclinical, Journal: Ryanodine receptor modulation by caffeine challenge modifies Na current properties in intact murine skeletal muscle fibres. (Pubmed Central) - Nov 14, 2020
These effects precisely paralleled previous reports of persistently (~10 min) increased cytosolic [Ca] with 0.5 mM, and an early peak rapidly succeeded by persistently reduced [Ca] likely reflecting gradual RyR inactivation with ≥1.0 mM caffeine. The latter findings suggested inhibitory effects of even resting cytosolic [Ca] on I. They suggest potentially physiologically significant negative feedback regulation of RyR activity on Na1.4 properties through increased or decreased local cytosolic [Ca], Ca-calmodulin and FKBP12.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma, Nimotop (nimodipine) / Bayer
Preclinical, Journal: Significant reduction of vascular reactivity with dantrolene and nimodipine in diabetic rats: a potential approach to cerebral vasospasm management in diabetes. (Pubmed Central) - Nov 2, 2020
The objective was to evaluate the efficacy and safety of dantrolene sodium for injectable suspension (Ryanodex®) (DSS) for the treatment of EHS, administered as an adjunct to body cooling (BC). Improved endothelial-dependent relaxation and reduced vascular contractility with dantrolene are dose dependent. Thus, although dantrolene appears to be a promising alternative for the treatment of CVSPs when added to conventional therapies, careful titration should be performed to achieve a significant reduction in vascular hyperreactivity. Moreover, if our findings with rats are applicable to humans, the combined use of dantrolene and nimodipine at optimal doses may reduce CVSPs, especially in the diabetic population.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Ryanodine receptors drive neuronal loss and regulate synaptic proteins during epileptogenesis. (Pubmed Central) - Oct 30, 2020
Notably, dantrolene promoted neuroprotective effects by decreasing neuronal cell loss in CA1 and CA3, which explains the increased levels of synaptic proteins, and the apparent lack of positive effect on pathological plasticity. Taken together, our results revealed that RyRs may have a major role in the hippocampal neurodegeneration associated to the development of acquired epilepsy.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
[VIRTUAL] Malignant Syndrome: Perioperative Management Of The Parkinsonian Patient () - Oct 17, 2020 - Abstract #ASA2020ASA_1529;
Initial treatment with hydration, cooling, and dantrolene reversed his condition, followed by the eventual resumption of dopaminergic drugs. The triad of fever, severe rigidity, and altered sensorium should prompt evaluation for malignant syndrome in Parkinson's disease, consideration for urgent neurology consultation, and immediate treatment with dantrolene and dopaminergic drugs.
- |||||||||| citalopram / Generic mfg.
[VIRTUAL] Post-operative Management Of Patient With Fever, Muscle Rigidity, Tachycardia, Altered Mental Status () - Oct 17, 2020 - Abstract #ASA2020ASA_1488;
After uneventful intraoperative course, notable for fentanyl and haloperidol administration, patient was taken to PACU and found to have tachycardia, hyperthermia, altered mental status, muscle rigidity, and hypercarbia...Patient was admitted to Surgical ICU, ventilated with BiPAP, given fluids and dantrolene. Neurologic status and vital signs returned to normal within 24 hours.
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