- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Dantrolene : From Malignant Hyperthermia to Alzheimer's Disease. (Pubmed Central) - Sep 26, 2020
However the therapeutic effects are not consistent. In this review, we focus on the relationship between the altered RyR expression and function and the pathogenesis of AD, and the potential application of dantrolene as a novel treatment for the disease.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Review, Journal: Inhalational analgosedation in the intensive care unit : Risk of malignant hyperthermia (Pubmed Central) - Sep 26, 2020
In this review, we focus on the relationship between the altered RyR expression and function and the pathogenesis of AD, and the potential application of dantrolene as a novel treatment for the disease. Consequences of an MH crisis for doctors, patients, and relatives regarding patient rights legislation, as well as insurance and employment issues with respect to the German Genetic Diagnostics Act are discussed.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
[VIRTUAL] TRPA1 Channels Are a Source of Calcium-driven Cellular Mechano-arrhythmogenicity (OnDemand) - Sep 17, 2020 - Abstract #AHA2020AHA_3078;
Drugs were used to buffer Ca2+ (BAPTA), stabilise RyR (dantrolene), non-selectively block stretch-activated channels (streptomycin), or specifically block (HC-030031) or activate (AITC) mechano-sensitive TRPA1 channels... TRPA1 activation increases mechano-arrhythmogenicity via a Ca2+-driven mechanism and may represent a novel anti-arrhythmic target in pathologies involving altered cardiac mechanics.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Molecular mechanisms of caffeine-mediated intestinal epithelial ion transports. (Pubmed Central) - Sep 2, 2020
Caf stimulates intestinal anion secretion mainly through the RyR/Orai1/Ca signaling, and there is a synergism of cAMP/PKA and Caf/Ca -mediated anion secretion. Our findings implicate that Caf-mediated RyR/Orai1/Ca pathway could be novel potential drug targets to control intestinal anion secretion.
- |||||||||| bromocriptine / Generic mfg.
Clinical, Journal: Neuroleptic Malignant Syndrome or Catatonia? A Case Report. (Pubmed Central) - Sep 1, 2020
Early recognition and management of NMS and MC in a complex, gravely ill patient, may be accomplished in the ICU despite obfuscation of traditional signs and symptoms of the NMS and MC syndrome. Such interventions can have life-saving effects on patients in danger of fatal autonomic instability.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines. (Pubmed Central) - Aug 18, 2020
The resulting guidelines are based on available evidence and the opinions of international malignant hyperthermia experts representing a large group of malignant hyperthermia laboratories from around the world. Key recommendations include: the dosing regimen of dantrolene should be based on actual body weight, dantrolene should be available wherever volatile anaesthetics or succinylcholine are used, and 36 vials of dantrolene should be immediately available with a further 24 vials available within 1 h.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
[VIRTUAL] Drug library screen identifies inhibitors of toxic astrogliosis () - Aug 16, 2020 - Abstract #MSDC2020MSDC_995;
Dantrolene, an anti-spasticity drug that inhibits calcium release through ryanodine receptors (RyR) expressed in the ER of CNS cells, also exerted inhibitory effect at in vivo-achievable concentrations. We also established CSF SERPINA3 as a relevant pharmacodynamic marker for inhibiting toxic astrocytes in clinical trials.Conclusions In conclusion, drug library screening provides mechanistic insight into generation of toxic astrocytes and identifies candidates for immediate proof-of-principle clinical trial(s).
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Memory and Learning Deficits Are Associated With Ca Dyshomeostasis in Normal Aging. (Pubmed Central) - Aug 9, 2020
In vivo, both middle-aged and aged mice showed cognitive deficits compared to young mice, which improved after dantrolene treatment. These findings support the hypothesis that intracellular Ca dyshomeostasis is a major mechanism underlying the cognitive deficits seen in both normal aging and degenerative neurologic diseases.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Phase classification, Trial completion date, Trial initiation date, Trial primary completion date: A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias. (clinicaltrials.gov) - Aug 7, 2020
P2/3, N=84, Not yet recruiting,
These findings support the hypothesis that intracellular Ca dyshomeostasis is a major mechanism underlying the cognitive deficits seen in both normal aging and degenerative neurologic diseases. Phase classification: P1 --> P2/3 | Trial completion date: Feb 2020 --> Jun 2023 | Initiation date: Oct 2019 --> Oct 2020 | Trial primary completion date: Feb 2020 --> Jun 2023
- |||||||||| venlafaxine / Generic mfg., risperidone / Generic mfg., Egis, quetiapine / Generic mfg.
[VIRTUAL] Quetiapine induced neuroleptic malignant syndrome (Poster Area) - Aug 5, 2020 - Abstract #ECNP2020ECNP_754;
Thereafter, treatment with quetiapine, lithium and venlafaxine was discontinued and treatment with intravenous fluids, diazepam and dantrolene was initiated...He was then medicated with lorazepam 2.5 mg three times daily, and after 3 days of continued improvement, lithium was reintroduced (800 mg/day)...He was ultimately transferred to a Psychiatric ward where venlafaxine 150 mg was reintroduced and risperidone was later initiated (slowly titled until 2 mg per day), with an improvement of the depressive and psychotic symptoms, without the development of NMS signs during the internment and on the next months of follow up...Moreover, NMS as already been associated with other drugs, namely mood stabilizers and antidepressants, and that´s why lithium and venlafaxine were also initially discontinued. This case highlights that one should always be watchful to the signs of NMS, even in patients taking antipsychotics rarely associated with this syndrome.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
[VIRTUAL] Lysosome-autophagosome defects mediate proteinopathy in early stages of Alzheimers disease () - Aug 2, 2020 - Abstract #AAIC2020AAIC_410;
Prior to overt histopathology or cognitive deficits, decreased V-ATPase expression on acidic compartments and increased autophagosomes in 3xTg-AD mice reflects impaired lysosomal activity, which is mediated through upstream RyR-Ca2+ dyshomeostatis. Increased RyR-mediated Ca2+ release alkalizes lysosomes pH resulting in abnormal intracellular protein aggregates, demonstrating that aberrant intracellular Ca2+ signaling in early AD disrupts autophagy and protein clearance.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Dopamine induces release of calcium from internal stores in layer II lateral entorhinal cortex fan cells. (Pubmed Central) - Jul 29, 2020
Dopamine also induced calcium transients in fan cells when calcium was excluded from the extracellular medium, further indicating that the calcium transients are linked to release from internal stores. These results indicate that following D-like-receptor binding, dopamine selectively induces transient elevations in intracellular calcium via activation of IP and ryanodine receptors, and that these elevations are linked to the facilitation of synaptic responses in putative layer II entorhinal cortex fan cells.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Clinical, Journal: Acute postoperative sepsis mimicking symptomology suspicious for malignant hyperthermia: case report (Pubmed Central) - Jul 29, 2020
While sepsis rapidly progresses to secondary injuries, malignant hyperthermia is life threatening. Providing ideal care requires good clinical judgment and a high level of suspicion where timely and appropriate care such as early administration of dantrolene and consultation of malignant hyperthermia association hotline for added assistance can influence positive outcomes.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: A Novel Recessive TNNT1 Congenital Core-Rod Myopathy in French Canadians. (Pubmed Central) - Jul 29, 2020
Providing ideal care requires good clinical judgment and a high level of suspicion where timely and appropriate care such as early administration of dantrolene and consultation of malignant hyperthermia association hotline for added assistance can influence positive outcomes. This study expands the phenotypic spectrum of TNNT1 myopathy and provides functional evidence for the pathogenicity of the newly identified missense mutation.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Clinical, Journal: Almost-certain malignant hyperthermia during cardiopulmonary bypass: a case report and literature review. (Pubmed Central) - Jul 25, 2020
Although dantrolene and corresponding treatments were administered recently, the patient died 12 days after surgery because of acute kidney failure and cardiac arrest. Therefore, it is important for us to previously recognize some specific signs of malignant hyperthermia during cardiopulmonary bypass to avoid severe outcomes.
- |||||||||| memantine / Generic mfg.
Review, Journal: Harnessing ionic mechanisms to achieve disease modification in neurodegenerative disorders. (Pubmed Central) - Jul 22, 2020
In this view, mounting evidence points to ionic mechanisms (IMs) as targets with potential therapeutic efficacy across distinct NDD subtypes. The scope of this review is to present clinical and preclinical evidence supporting the link between disruption of IMs and neuronal death in specific NDDs and to critically revise past and ongoing attempts of harnessing IMs for the development of neuroprotective treatments.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer's Disease. (Pubmed Central) - Jul 16, 2020
Dantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer's disease patients. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Overactivation of ryanodine receptors in the endoplasmic reticulum and the resulting dysregulation of calcium homeostasis contribute to Alzheimer's disease-related pathophysiologyDantrolene is an antagonist of ryanodine receptors, and its chronic use has been suggested to improve memory function in experimental models of Alzheimer's disease WHAT THIS ARTICLE TELLS US THAT IS NEW: Survival, proliferation, and differentiation of neuronal progenitors derived from patients with Alzheimer's disease are impaired when compared with healthy counterpartsChronic exposure of induced pluripotent stem cells, derived from patients with Alzheimer's disease, to dantrolene improves the survival, proliferation, and differentiation of these cells.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma, sulfasalazine / Generic mfg., warfarin / Generic mfg.
[VIRTUAL] Mesalamine Induced Eosinophilic Pleural Effusion (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_5239;
Multiple medications have been associated with the development of EPE, including mesalamine, warfarin, dantrolene, and valproic acid. In cases of EPE with unclear etiology despite extensive workup, patient's medications list should be reviewed to rule out medications induced EPE.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma, lorazepam / Generic mfg.
[VIRTUAL] 2,4 DNP, A Lethal Slimming Pill (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_3056;
Within a few minutes of arrival to ER, the patient became extremely agitated and had to be given 8 mg of lorazepam in 2 doses and was later intubated...Fever and diaphoresis should be promptly treated with active cooling measures such as cooling blankets, IV Tylenol and Dantrolene can be considered if first line cooling measures fail...Because of extremely high mortality, an intensive approach should be adopted early in symptomatic patients who present after taking a potentially fatal dose. These patients should be managed in ICU with early intubation and mechanical ventilation and physicians should be aware that deterioration can be rapidly fatal.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: Intranasal administration of dantrolene increased brain concentration and duration. (Pubmed Central) - Jun 25, 2020
Blood brain barrier pump inhibitors did not further increase dantrolene peak concentrations in the brain. Our results suggested that Intranasal administration of dantrolene is an effective route to increase its concentration and duration in the brain compared to the oral approach, without any obvious side effects on olfaction or motor function.
- |||||||||| danazol oral / Generic mfg.
Journal: Application of a refined Developability Classification System. (Pubmed Central) - May 13, 2020
The rDCS was able to predict the results in humans correctly in 80% of cases. Overall, the results suggest that the rDCS is a highly useful tool for estimating the in vivo behaviour of new drug candidates.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: PHENYTOIN REDUCES ACTIVITY OF RYR2 - A POTENTIAL MECHANISM FOR ITS CARDIOPROTECTIVE ACTION. (Pubmed Central) - May 6, 2020
SIGNIFICANCE STATEMENT: We show that phenytoin, a Na channel blocker used clinically for treatment of epilepsy, is a diastolic inhibitor of cardiac calcium release channels (RyR2) at doses 3-fold lower than its current therapeutic levels. Phenytoin inhibits RyR2 from failing human heart and not from healthy heart indicating that phenytoin may selectively target defective RyR2 channels in humans, pointing to phenytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardiac arrhythmias.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Ryr2 Inhibition By Dantrolene Can Attenuate Pressure-overload Induced Cardiac Hypertrophy (Poster Hall) - Apr 22, 2020 - Abstract #RHYTHM2020RHYTHM_204;
TRPA1 may represent a novel anti-arrhythmic target in pathologies involving altered mechanics and Ca2+ dynamics. RyR2 inhibition can attenuate cardiac remodeling induced by pressure overload, and the potential mechanism may associated to calcium-handling related inflammation and metabolism changes.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Journal: The current status of malignant hyperthermia. (Pubmed Central) - Apr 20, 2020
Dantrolene is the only available drug approved for the treatment of MH through suppressing the calcium release from SR...Therefore, it is very important for anesthesiologists to raise awareness and understand the characteristics of MH. This review summarizes epidemiology, clinical symptoms, diagnosis and treatments of MH and any new developments.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Clinical, Journal: A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer's Disease. (Pubmed Central) - Apr 18, 2020
Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma, dalfampridine / Generic mfg., PD98059 / Wayne State University
Preclinical, Journal: 11-Keto-β-Boswellic Acid Attenuates Glutamate Release and Kainic Acid-Induced Excitotoxicity in the Rat Hippocampus. (Pubmed Central) - Apr 17, 2020
In a rat model of excitotoxicity induced by intraperitoneal kainic acid injection (15 mg/kg), intraperitoneal 11-keto-β-boswellic acid administration (10 or 50 mg/kg) 30 min before kainic acid injection considerably ameliorated kainic acid-induced glutamate concentration elevation and CA3 neuronal death. These data suggested that 11-keto-β-boswellic acid inhibits glutamate release from the rat hippocampal synaptosomes by suppressing N- and P/Q-type Ca channels and protein kinase A activity, as well as exerts protective effects against kainic acid-induced excitotoxicity in vivo.
- |||||||||| Ryanodex (dantrolene) / Eagle Pharma
Trial completion, Trial completion date, Trial primary completion date: A Clinical Trial Utilizing Dantrolene in Patients with Ventricular Arrhythmias. (clinicaltrials.gov) - Apr 8, 2020
P1, N=5, Completed,
These data suggested that 11-keto-β-boswellic acid inhibits glutamate release from the rat hippocampal synaptosomes by suppressing N- and P/Q-type Ca channels and protein kinase A activity, as well as exerts protective effects against kainic acid-induced excitotoxicity in vivo. Recruiting --> Completed | Trial completion date: Jul 2020 --> Feb 2020 | Trial primary completion date: Jun 2020 --> Feb 2020
- |||||||||| tacrolimus / Generic mfg., cyclophosphamide intravenous / Generic mfg.
Review, Journal: Treatment of Satoyoshi syndrome: a systematic review. (Pubmed Central) - Mar 31, 2020
Further studies are needed to determine optimal dose and duration of corticosteroids as well as the role of other immunosuppressants and immunoglobulin therapy. Genetic or autoimmune markers will be useful to guide future therapies.
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