Disease relevance of dantrolene

• Treatment of heat stroke with dantrolene [1].
• Dantrolene, pelvic neoplasm, and muscle spasms: report of a case [2].
• Letter: Treatment of spasticity in multiple sclerosis with dantrolene [3].
• Letter: Dantrolene in amyotrophic lateral sclerosis [4].
• Treatment of neuroleptic malignant syndrome with dantrolene [5].

Psychiatry related information on dantrolene

• Dantrolene in lethal catatonia [6].
• The addition of dantrolene (response time, 1.15 days) or bromocriptine (response time, 1.03 days) significantly shortened the time to clinical response [7].
• Treatment of lethal catatonia with electroconvulsive therapy and dantrolene sodium: a case report [8].
• Letter: Hallucinations associated with dantrolene sodium therapy [9].

High impact information on dantrolene

• Calcium release from skeletal muscle sarcoplasmic reticulum: site of action of dantrolene sodium [10].
• Dantrolene sodium markedly suppresses the release of calcium previously sequestered by skeletal, but not cardiac, muscle sarcoplasmic reticulum [10].
• Letter: Dantrolene deposited in connective tissue [11].
• Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil [12].
• This study demonstrated that exertional rhabdomyolysis is associated with elevated [Ca2+]i, and that dantrolene has a beneficial effect in this syndrome [13].

Chemical compound and disease context of dantrolene

• Dantrolene reduces the elevated myoplasmic Ca(2+) generated during malignant hyperthermia, a pharmacogenetic crisis triggered by volatile anesthetics [14].
• Phenelzine toxicity responsive to dantrolene [15].
• Intravenous injection of levodopa is more effective than dantrolene as therapy for neuroleptic malignant syndrome [16].
• It turned out that dantrolene, even under conditions allowing Ca2+ influx, inhibited toxicity induced by QA, NMDA, and glutamate, whereas that induced by AMPA or KA was unaffected [17].
• Because it is likely that glutamate is involved in neuronal degeneration associated with ischemia and hypoxia, the present findings might suggest that dantrolene and possibly other drugs affecting intracellular calcium pools might be of therapeutic interest [18].

Biological context of dantrolene

• Phosphorylation of all NARPPs was eliminated by dantrolene, which inhibits release of calcium from intracellular stores [19].
• Identification of dantrolene binding sites in porcine skeletal muscle sarcoplasmic reticulum [20].
• To explore its mechanism of action, the effect of dantrolene on MH-like channel activation by the synthetic domain peptide DP4 or anti-DP4 antibody was examined [21].
• In an insult that exhibited secondary energy failure and apoptosis we identified a relative 25% augmentation of high-energy phosphates at the end of recovery when the ryanodine-receptor antagonist, dantrolene, was introduced in the early (0- to 40-minute) but not late (40- to 120-minute) stage of recovery (P < 0.05) [22].
• Early postischemic dantrolene-induced amelioration of poly(ADP-ribose) polymerase-related bioenergetic failure in neonatal rat brain slices [22].

Anatomical context of dantrolene

• Dantrolene diminishes the activation of the contractile process in muscle fibers by reducing the release of calcium ions from the sarcoplasmic reticulum [23].
• The lowered excitotoxic threshold for kainic acid was also observed in mice transgenic for mutant human PS2[N141I] and was prevented by dantrolene, an inhibitor of Ca(2+) release from the endoplasmic reticulum [24].
• Monitored in cells expressing appropriately targeted aequorins, dantrolene, an inhibitor of RyR I channels, elevated free Ca(2+) concentrations in the secretory vesicle compartment from 40.1 +/- 6.7 to 90.4 +/- 14.8 microm (n = 4, p < 0.01), while having no effect on ER Ca(2+) concentrations [25].
• Effects of dantrolene, a blocker of intracellular Ca2+ release, on the oscillation of the intracellular Ca2+ ([Ca2+]i) induced by caffeine were studied in bullfrog sympathetic ganglion cells, using a Fura-2 fluorescence technique [26].
• Angiotensin II (AII) regulates the secretion of aldosterone from adrenal glomerulosa cells by a calcium-dependent mechanism which involves both the uptake of calcium from the extracellular pool, and the release of calcium from a dantrolene-sensitive intracellular pool [27].

Associations of dantrolene with other chemical compounds

• The release of Ca2+ from this pool is sensitive to the skeletal muscle relaxant dantrolene, and this may constitute a novel and alternative therapeutic approach against NMDA receptor-mediated excitotoxicity [28].
• In contrast, cardiac sarcoplasmic reticulum vesicle 45Ca2+ release and [3H]ryanodine binding were unaffected by dantrolene [29].
• Because dantrolene strongly inhibited glucose-stimulated insulin secretion (from 3.07 +/- 0.51-fold stimulation to no significant glucose effect; n = 3, p < 0.01), we conclude that RyR I-mediated Ca(2+)-induced Ca(2+) release from secretory vesicles, possibly potentiated by NAADP, is essential for the activation of insulin secretion [25].
• Because 2-APB inhibits hyphal growth and dissipates the tip-high cytosolic [Ca(2+)] gradient, whereas heparin microinjection, TMB-8 and dantrolene treatments do not affect growth, we suggest that the small conductance channel generates the obligatory tip-high Ca(2+) gradient during hyphal growth [30].
• [3H]-ryanodine binding in total membranes was enhanced by AMP-PCP, caffeine and xanthine, whereas Mg2+, Ruthenium Red and dantrolene were inhibitors [31].

Gene context of dantrolene

• However, the molecular basis and specificity of the actions of dantrolene on RYR channels have remained in question [32].
• In contrast to the RYR1 isoform, the cardiac RYR2 isoform was unaffected by dantrolene, both in native cardiac SR vesicles and when heterologously expressed in HEK-293 cells [32].
• Our results thus indicate that both the RYR1 and the RYR3, but not the RYR2, may be targets for dantrolene inhibition in vivo [32].
• Dantrolene decreased TNF-alpha in lung (26.1%), liver (29.4%), and spleen (35.4%) (p < .05) and IL-1 alpha in lung (30.0%) and liver (25.4%) (p < .05) [33].
• In addition, both ruthenium red and dantrolene had a strong inhibitory effect on IL-2-dependent proliferation of CTLL-2 T cells [34].

Analytical, diagnostic and therapeutic context of dantrolene

• To determine if [Ca2+]i is responsible for the major metabolic changes which are hallmarks of sepsis, we examined if sodium dantrolene, a drug which decreases release of calcium from sarcoplasmic reticulum, affected the metabolic abnormalities in plasma and epitrochlearis muscles of rats made septic by cecal ligation and perforation [35].
• We report the identification of specific dantrolene binding sites in porcine skeletal muscle sarcoplasmic reticulum using a rapid filtration binding assay for [3H]dantrolene [20].
• In each case liver function tests returned to normal after withdrawing treatment with dantrolene [36].
• Perfusion of 1 mM dantrolene + ACPD inhibited the ACPD-evoked increase in [14C]-L-citrulline recovery [37].
• The prompt and satisfactory outcome after early diagnosis indicates that dantrolene should be considered a useful treatment in NMS [38].

References