Dantrolene – A review of its pharmacology, therapeutic use and new developments

@article{Krause2004DantroleneA,
  title={Dantrolene – A review of its pharmacology, therapeutic use and new developments},
  author={T Krause and Mark Ulrich Gerbershagen and Marko Fiege and Ralf Weisshorn and Frank Wappler},
  journal={Anaesthesia},
  year={2004},
  volume={59}
}
Human malignant hyperthermia is a life‐threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses… 

Dantrolene : From Malignant Hyperthermia to Alzheimer's Disease.

This review focuses 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.

Effects of azumolene on normal and malignant hyperthermia-susceptible skeletal muscle.

Investigation of the potency of azumolene, a 30-fold more water-soluble analogue, in comparison to the prototype dantrolene sodium, on mammalian and human skeletal muscles and in vitro exposure of mouse soleus muscle provides evidence that azuolene is equipotent to dantroene sodium in blocking pharmacologic-induced muscle contractures and that azumaolene should be efficacious for treatment/prevention of malignant hyperthermia.

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent

Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo.

Malignant hyperthermia

  • Dong-Chan Kim
  • Medicine, Biology
    Korean journal of anesthesiology
  • 2012
The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS.

Malignant hyperthermia and associated conditions.

Malignant hyperthermia: current strategies for effective diagnosis and management

A novel nanocrystalline dantrolene sodium suspension (DSS) was shown to be as effective as the standard dantrogene preparation without relevant side effects and enables a faster administration of dantrole and consequently hastens treatment of a crisis.

Malignant hyperthermia in dogs during general anaesthesia

Alternative drugs such as a cepromazine, diazepam and alfentanil to be used for the treatment of clinical findings manifested during malignant hyperthermia .

Clinical protocol for the management of malignant hyperthermia.

...

References

SHOWING 1-10 OF 104 REFERENCES

Identification of Dantrolene Binding Sites in Porcine Skeletal Muscle Sarcoplasmic Reticulum (*)

It is suggested that dantrolene inhibits calcium release from the sarcoplasmic reticulum by either direct or indirect interaction with the ryanodine receptor.

Pharmacological distinction between dantrolene and ryanodine binding sites: evidence from normal and malignant hyperthermia-susceptible porcine skeletal muscle.

The characteristics of dantrolene binding to porcine malignant-hyperthermia-susceptible and normal-skeletal-muscle SR are compared, and the effects of RyR modulators on [3H]dantrolenes binding to these membranes are examined, suggesting that the binding sites for these two drugs are pharmacologically distinct, and may exist on separate molecules.

Dantrolene Sodium Can Increase or Attenuate Activity of Skeletal Muscle Ryanodine Receptor Calcium Release Channel: Clinical Implications

The study results suggest that at least two binding sites for DS exist on the Ry1 receptor calcium channel, and a low‐affinity (micro Meter) site is associated with reduced channel gating and open‐state dwell time and may relate to the established pharmacologic muscle relaxant effect of DS.

Rationale for dantrolene vs. procainamide for treatment of malignant hyperthermia.

Dantrolene was effective in preventing or reversing the abnormal halothane-induced contracture response of human MHS muscle strips and the lack of effectiveness of procainamide in the treatment of malignant hyperthemia.

An update on the malignant hyperthermia syndrome.

The understanding of the molecular genetics of MH is hoped to lead to a simpler diagnostic test than is currently available, and enhance the understanding of MH and its relation to other myopathies.

Identification of a Dantrolene-binding Sequence on the Skeletal Muscle Ryanodine Receptor*

The results indicate that synthetic domain peptides can mimic a native, ligand-binding conformation in vitro and that the dantrolene-binding site and the epitope for the monoclonal antibody on RyR1 are equivalent and composed of amino acids 590–609.

Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia

Co-segregation of MH with RYRmarkers, resulting in a lod score of 4.20 at a linkage distance of zero centimorgans, indicates that MH is likely to be caused by mutations in the RYR gene.

Effects of Dantrolene on Steps of Excitation-Contraction Coupling in Mammalian Skeletal Muscle Fibers

Dantrolene was found to suppress the depolarization-induced elevation in intracellular calcium concentration ([Ca2+]i) by inhibiting the release of calcium from the SR by binding on the SR membrane, but be distinct from the purified RYR itself.

Genetics and pathogenesis of malignant hyperthermia

As a result of extensive research on the mechanisms of excitation‐contraction coupling and recent functional characterization of several disease‐causing mutations in heterologous expression systems, much is known about the molecular etiology of MH.

Dantrolene Inhibition of Ryanodine Receptor Ca2+Release Channels

The results indicate that both the RYR1 and the RYP3, but not the Ryr2, may be targets for dantrolene inhibitionin vivo.
...