ライフサイエンスコーパス: dantrolene

1 reversible by a ryanodine receptor blocker (dantrolene).

2 g the patch seal or with RyR block by 10 muM dantrolene.

3 Calpain expression was reduced by dantrolene.

4 d that ATP enhanced the inhibiting effect of dantrolene.

5 doplasmic reticulum (ER) that was blocked by dantrolene.

6 and [3H]ryanodine binding were unaffected by dantrolene.

7 ented by cotreatment with the RyR1 inhibitor dantrolene.

8 solubility and rapid clearance in vivo over dantrolene.

9 ed by exposure to ryanodine receptor blocker dantrolene.

10 block, modulation by ATP, and inhibition by dantrolene.

11 ]i, ROS, and DDR signals are normalized with dantrolene.

12 th a novel formulation of the RyR inhibitor, dantrolene.

13 (+3) or GsMTx-4 and completely suppressed by dantrolene.

14 r of calcium-induced calcium release (CICR), dantrolene.

15 on response was reduced by ruthenium red and dantrolene.

16 se of Ca(2+) in a manner paralleling that of dantrolene.

17 after exposure to clinical concentrations of dantrolene.

18 + exchange and subsequent Na+-Ca2+ exchange; dantrolene (10 mg/kg, 30 mins, 6 and 22 hrs postburn) to

19 nhibition of the pig skeletal muscle RYR1 by dantrolene (10 microm) was associated with a 3-fold incr

20 + ionophore (A23187), nifedipine (1 microM), dantrolene (10 microM), thapsigargin (100 nM), or L-glut

21 hed by further addition of the RyR-inhibitor dantrolene (10 uM).

22 ble by either wortmannin (1.5 micromol/l) or dantrolene (12.5 micromol/l).

23 RyR) antagonist ruthenium red (10 microM) or dantrolene (25 microM) inhibited the HP-induced calcium

24 Finally, FAT defects are prevented by dantrolene, a clinical compound that reduces Ca(2+) rele

25 l death of 58Q PC cultures was attenuated by dantrolene, a clinically relevant RyanR inhibitor and Ca

26 at feeding SCA3-YAC-84Q transgenic mice with dantrolene, a clinically relevant stabilizer of intracel

27 Dantrolene, a drug used to treat MH, binds to a region w

28 Isoflurane cytotoxicity was suppressed by dantrolene, a ryanodine receptor antagonist that inhibit

29 sepsis was blocked by treating the rats with dantrolene, a substance that inhibits the release of cal

30 The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chym

31 Dantrolene abrogated the ethanol-induced acceleration of

32 team approach with specific management using dantrolene, active cooling, and hyperventilation.

33 +) from MgATP hydrolysis is required to make dantrolene administration effective in arresting an MH e

34 The inducibility of VF after dantrolene administration was documented.

35 In rats challenged with endotoxin, dantrolene affected neither survival nor circulating con

36 l rats were randomized to receive vehicle or dantrolene after intravenous injection of endotoxin.

37 that long-term feeding of SCA1-58Q mice with dantrolene alleviated age-dependent motor deficits (quan

38 In diabetic rats, 10 uM of dantrolene alone failed to reduce 5-HT-induced maximal c

39 In contrast, challenge by dantrolene alone left both currents and their parameters

40 Dantrolene also inhibited [3H]ryanodine binding to purif

41 Animal studies suggest that dantrolene also protects against heart failure and arrhy

42 ism of dantrolene's action and suggests that dantrolene also requires ATP to inhibit RyR.

43 However, dantrolene (an inhibitor of Ca(2+)-dependent Ca2+ releas

44 stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffein

45 Here we show that azumolene, an equipotent dantrolene analog, inhibits a component of SOCE coupled

46 gin D, and the ryanodine receptor inhibitors dantrolene and 1,1'-diheptyl-4,4'-bipyridinium dibromide

47 or-alpha secretion by myocytes; in contrast, dantrolene and amiloride provided significantly greater

48 Dantrolene and BAPTA-AM prevented the increase in intrac

49 locked by the ryanodine receptor inhibitors, dantrolene and DHBP.

50 tions of these results for understanding how dantrolene and malignant hyperthermia mutations may affe

51 experiments demonstrated that the effect of dantrolene and Mg(2+) was cooperative and that ATP enhan

52 suggest that simultaneous administration of dantrolene and nimodipine has a synergistic effect in re

53 In addition, concomitant administration of dantrolene and nimodipine reduced vascular reactivity to

54 ss of compounds, we test the hypothesis that dantrolene and phenytoin have similar inhibitory effects

55 nced by caffeine, whereas it is inhibited by dantrolene and ruthenium red, two blockers of calcium-in

56 The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER

57 action compared with the pan-RyR inhibitors dantrolene and tetracaine and the antiarrhythmic drug fl

58 Dantrolene and thapsigargin, which decrease intracellula

59 ombination of the ryanodine receptor blocker dantrolene and the Ca2+ channel blocker nimodipine signi

60 n DA release was prevented by a RyR blocker, dantrolene, and by CPA.

61 erminus of the RyR is a molecular target for dantrolene, and suggest a regulatory role for both n-cal

62 HEK-293 cells was significantly inhibited by dantrolene, and the extent of RYR3 inhibition was simila

63 N2a cells was blocked by either ryanodine or dantrolene, antagonists of Ryrs and by Genz-161, a gluco

64 ion, such as clinical studies of repurposing dantrolene as a potential new therapy for heart failure

65 These activities were inhibited by dantrolene at 37 degrees C, yet required the presence of

66 significantly worse among rats that received dantrolene at a dose of 10 mg/kg, irrespective of whethe

67 This increase was reversed by dantrolene at both 37 and 22 degrees C and was unaffecte

68 inhibiting only RyR1 and RyR3 with 25 microM dantrolene attenuated these responses caused by high (>5

69 ected by the presence of dantrolene but that dantrolene becomes increasingly effective as cytoplasmic

70 Intraperitoneal bolus dantrolene before HAL prolongs time to respiratory arres

71 Because phenytoin and dantrolene belong to the hydantoin class of compounds, w

72 in cleavage of the RyR does not affect [(3)H]dantrolene binding in the presence of AMP-PCP, but depre

73 [(3)H]Dantrolene binding to both the intact and the n-calpain-

74 d-binding conformation in vitro and that the dantrolene-binding site and the epitope for the monoclon

75 Although dantrolene binds to the RyR protein, its mechanism of ac

76 , the cardiac RYR2 isoform was unaffected by dantrolene, both in native cardiac SR vesicles and when

77 e of Mg(2+) is unaffected by the presence of dantrolene but that dantrolene becomes increasingly effe

78 This binding was displaced by caffeine and dantrolene, but not by ruthenium red, heparin or cyclic

79 gs (100 nM cytoplasmic [Ca(2+)] + 2 mM ATP), dantrolene caused inhibition of RyR1 (rabbit skeletal mu

80 calcium signalling stabilization, e.g. with dantrolene, could be a potential disease modifying thera

81 We conclude that dantrolene decreases survival in bacterial sepsis and ha

82 In non-diabetic rats, by contrast, dantrolene did not modify the vascular response to 5-HT.

83 tretraacetic acid (acetoxymethyl) ester, and dantrolene, did not alter bortezomib cytotoxicity.

84 Importantly, dantrolene diminishes Abeta load, reduces Abeta-related

85 f action has remained controversial, because dantrolene does not inhibit single ryanodine receptor (R

86 HF animals were randomized to receive dantrolene (DS) or placebo in early or chronic HF.

87 membrane potential of -70 mV) tetracaine and dantrolene each blocked IP3-evoked Ca2+ increases.

88 rcoplasmic reticulum (SR) vesicles such that dantrolene effectively reversed the 3-fold decrease in t

89 AN while neurones pretreated with 100 microM dantrolene failed to show potentiation of DeltaVCAN when

90 henytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardi

91 henytoin as a more human-safe alternative to dantrolene for therapies against heart failure and cardi

92 Pretreatment with 40 microM dantrolene gave substantial protection against TG- or BH

93 Dantrolene, given with conventional cooling methods, off

94 of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04).

95 sure >/=60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0

96 0 s and 20 s, the generator potential of the dantrolene group is significantly greater than that of t

97 (group 1), conventional cooling methods and dantrolene (group 2), conventional cooling methods and d

98 In mouse cardiomyocytes, dantrolene had no effect on cardiac Ca(2+) release in th

99 (RYR) channels, the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental

100 dodantrolene, a photoactivatable analogue of dantrolene, has identified a 160 kDa SR protein with imm

101 VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Lang

102 Dantrolene improved function of livers preserved in Euro

103 We hypothesized that dantrolene improves survival after ventricular fibrillat

104 ggered by infections, which were relieved by dantrolene in 1 patient.

105 Treatment with dantrolene in 4L;C* mice starting at postnatal day 5 del

106 or a formal synthesis of the muscle relaxant Dantrolene in excellent yields.

107 tors that are consistent with the actions of dantrolene in vivo and suggest a mechanism of action in

108 In media simulating resting myoplasm, dantrolene increased the half-time for 45Ca2+ release fr

109 Interestingly, dantrolene-induced lowering of RyR-mediated Ca(2)(+) rel

110 Dantrolene infusion during cardiopulmonary resuscitation

111 se of the controversial results showing that dantrolene inhibited Ca(2+) release from intact fibers a

112 Dantrolene inhibited RyR2 with an IC50 of 0.16 +/- 0.03

113 e RYR3, but not the RYR2, may be targets for dantrolene inhibition in vivo.

114 oration into lipid bilayers, is required for dantrolene inhibition of RyR channels.

115 We conclude that CaM is essential for dantrolene inhibition of RyR1 and RyR2.

116 strated, there is little evidence for direct dantrolene inhibition of RyR1 channel function.

117 Its absence explains why dantrolene inhibition of single RyR channels has not bee

118 Dantrolene inhibition of the RYR1 was dependent on the p

119 Mutant N98S-CaM facilitated dantrolene inhibition with an IC50 = 5.9 +/- 0.3 nM.

120 ly attenuated by co-injecting BAPTA, heparin/dantrolene (inhibitors of intracellular Ca2+ release), a

121 Although dantrolene inhibits Ca(2+) release from the sarcoplasmic

122 Dantrolene inhibits the high potassium-induced release o

123 The skeletal muscle relaxant dantrolene inhibits the release of Ca2+ from the sarcopl

124 ults suggest that the mechanism of action of dantrolene involves stabilization of domain-domain inter

125 Dantrolene is a drug that suppresses intracellular Ca(2+

126 Dantrolene is a ryanodine receptor (RyR) inhibitor, whic

127 Dantrolene is a skeletal muscle relaxant which acts by i

128 Dantrolene is administered to alleviate MH symptoms, but

129 Unfortunately, dantrolene is hepatotoxic and unsuitable for chronic lon

130 Dantrolene is neuroprotective in animal models and may a

131 Dantrolene is the drug of choice for the treatment of ma

132 Dantrolene is the first line therapy of malignant hypert

133 ively, and define the mechanism of action of dantrolene is to increase the Mg(2+) affinity of the RyR

134 feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH.

135 o and suggest a mechanism of action in which dantrolene may act directly at the skeletal muscle ryano

136 nd that Ca(2+) signaling stabilizers such as dantrolene may be considered as potential therapeutic dr

137 Inhibition of RyR2 hyperactivity with dantrolene mitigates the vicious cycle of sarcoplasmic C

138 c rats after a 30-min incubation period with dantrolene, nimodipine, and both drugs in combination.

139 of a high-affinity, monophasic inhibition by dantrolene of ryanodine receptor Ca2+ channel function i

140 The inhibitory potency of dantrolene on ECCE found in wild-type and MH-susceptible

141 The effect of dantrolene on light adaptation of the photoreceptor was

142 plore its mechanism of action, the effect of dantrolene on MH-like channel activation by the syntheti

143 ular basis and specificity of the actions of dantrolene on RYR channels have remained in question.

144 ese results demonstrate selective effects of dantrolene on skeletal muscle ryanodine receptors that a

145 inding to further investigate the actions of dantrolene on the three mammalian RYR isoforms.

146 skeletal muscle function, but the effect of dantrolene on this pathway has not been examined.

147 Dantrolene or 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'-te

148 tation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset o

149 (benzodiazepines, dopamine agonists, and/or dantrolene) or electroconvulsive therapy, if indicated.

150 ernal stores by perifusion with ryanodine or dantrolene, or direct diffusion of Ruthenium Red into ce

151 hould malignant hyperthermia occur, however, dantrolene permits the dependable reversal of skeletal m

152 entional cooling or conventional cooling and dantrolene provided significant improvement in cardiovas

153 ity analogue in order to identify a putative dantrolene receptor in skeletal muscle.

154 Thus, the putative dantrolene receptor may be related to the skeletal muscl

155 the putative, intracellular, skeletal muscle dantrolene receptor.

156 Namely, 10 uM dantrolene reduced RyR channel open probability by ~50%

157 Dantrolene reduces the elevated myoplasmic Ca(2+) genera

158 king drugs such as ryanodine, tetracaine and dantrolene, reportedly specific inhibitors of RyRs.

159 ryanodine-sensitive stores (xestospongin and dantrolene, respectively) protected against the endanger

160 ling with the negative allosteric modulator, dantrolene (Ryanodex), restored vATPase levels, lysosoma

161 ts the direct, Mg(2+)-dependent mechanism of dantrolene's action and suggests that dantrolene also re

162 The current study examines the mechanisms of dantrolene's action on skeletal muscle and shows that on

163 t was concluded that an important factor for dantrolene's action was lost during the purification pro

164 ion on skeletal muscle and shows that one of dantrolene's mechanisms of action is to block excitation

165 (group 2), conventional cooling methods and dantrolene's vehicle mannitol (group 3), or no treatment

166 a; however, the molecular mechanism by which dantrolene selectively affects skeletal muscle Ca2+ regu

167 nhibiting Ca(2+)-dependent Ca2+ release from dantrolene-sensitive intracellular stores.

168 the apparently sequential activation of the dantrolene-sensitive, nonreceptor proline-rich tyrosine

169 ) elevated diastolic SR Ca(2+) leak that are dantrolene-sensitive.

170 ation of the site and mechanism of action of dantrolene should contribute to the understanding of the

171 ependent increase in capillary cell calcium, dantrolene significantly decreased hypoxia-induced capil

172 Administration of 20 mumol/L dantrolene significantly decreased spontaneous calcium e

173 nimodipine with the higher concentration of dantrolene significantly increased the EC(50) values for

174 Dantrolene significantly shortened the cooling time comp

175 Although dantrolene significantly shortened the cooling time, it

176 Dantrolene sodium is a medically important hydantoin der

177 eated intraperitoneal sepsis with the use of dantrolene sodium, a specific inhibitor of intracellular

178 we found that exposure to the RyR1 inhibitor dantrolene suppressed a similar component of charge move

179 Dantrolene suppressed the inhibitory effect of TNF on Bc

180 drugs that target ryanodine receptors (RyR1: dantrolene, tetracaine, S107) and L-type Ca(2+) channels

181 blocked by the RyR antagonists ryanodine and dantrolene, the calpain inhibitor calpastatin, and by a

182 Dantrolene, the only approved drug for MH, has the disad

183 Long-term feeding of the RyanR inhibitor dantrolene to amyloid precursor protein-presenilin-1 mic

184 up of nervous systems first was incubated in dantrolene to block release of calcium through the ryano

185 demonstrated to be the essential factor for dantrolene to inhibit Ca(2+) release in skinned muscle f

186 The effect of addition of dantrolene to preservation solutions on function of whol

187 Although specific binding of dantrolene to the type 1 ryanodine receptor (RyR1), the

188 he cortex and hippocampus is also reduced in dantrolene-treated AD mice.

189 in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007).

190 ntaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation

191 Dantrolene treatment did not appear to affect virus prod

192 patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca(2+) signalin

193 Furthermore, dantrolene treatment increased residual mutant GCase act

194 Dantrolene treatment partially normalized Ryr expression

195 Compared to untreated 4L;C* mice, dantrolene treatment significantly improved gait, reduce

196 AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and s

197 a coli and allocated to control, vehicle, or dantrolene treatment.

198 n of RyR-evoked calcium release with chronic dantrolene treatment.

199 Preincubation with azumolene, an analog of dantrolene used for the treatment of malignant hyperther

200 ase channel in SR, as a molecular target for dantrolene using the photoaffinity analog [(3)H]azidodan

201 hibition of vesicle [3H]ryanodine binding by dantrolene was associated with a decrease in the extent

202 Importantly, the efficacy of dantrolene was enhanced in low [Ca(2+)](o), suggesting a

203 found in human muscle susceptible to MH that dantrolene was ineffective at reducing halothane-induced

204 ng Ca(2+), ATP, Mg(2+) and the RyR inhibitor dantrolene were tested.

205 ge, effects abrogated by the RyR1-antagonist dantrolene which itself increased I(Na).

206 These adaptations were prevented by dantrolene, which blocks Ca2+ release from the SR.

207 Dantrolene, which depresses charge movement and E-C coup

208 sphorylation of all NARPPs was eliminated by dantrolene, which inhibits release of calcium from intra

209 nt of RCASBP M2C (4070A)-infected cells with dantrolene, which inhibits the release of calcium from t

210 lpain activity and ATP in the interaction of dantrolene with the RyR in vivo.

211 rdiac ryanodine receptor 2 (RyR2) inhibitor, dantrolene, without inhibiting Ca(2+) release during sys

212 Identification of the molecular target of dantrolene would greatly aid in understanding both the m