ライフサイエンスコーパス: flecainide

1 cation of the sodium channel-blocking agent, flecainide.

2 syndrome elicit proarrhythmic sensitivity to flecainide.

3 tically to the sodium channel blocking agent flecainide.

4 Ia and Ic antiarrhythmic drugs quinidine and flecainide.

5 ilure was rare in the quarter of patients on flecainide.

6 onths (3.8-5.3), ECG remained normal despite flecainide.

7 modes of action underlie RyR2 inhibition by flecainide.

8 ical activity with the Na(+) channel blocker flecainide.

9 ely than traditional Na+-channel blockade by flecainide.

10 ggested because of the hydrophilic nature of flecainide.

11 ic Scn5a+/- hearts treated with (1.0 microM) flecainide.

12 during exercise was significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for place

13 Flecainide (0.1 micromol/L) produced bidirectional condu

14 Flecainide 1 mumol/l was more effective in suppressing a

15 Flecainide (1 micromol/L) tonic block was only 16.8+/-3.

16 Flecainide (1-300 mM) caused tonic and use-dependent blo

17 In contrast, flecainide (10 muM) and thapsigargin (10 muM) eliminated

18 The median doses used were: flecainide 100 mg/m(2)/day (range: 40 to 150 mg/m(2)/day

19 ng propafenone 300 to 900 mg/day (n = 46) or flecainide 100 to 300 mg/day (n = 25), presented for ibu

20 entricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes).

21 aline (1 mg/kg), procainamide (10 mg/kg), or flecainide (2 mg/kg) on the ECG was studied in 34 patien

22 of either chloroquine (4 micromol/L, n=7) or flecainide (2-4 micromol/L, n=5).

23 mic drug treatment (control); treatment with flecainide (200-300 mg per day) for 4 weeks (short-term

24 Ca(2+) transients, which were unaffected by flecainide (6 mumol/L).

25 the combination of a Na(+) channel blocker (flecainide, 7 micromol/L) and acetylcholine (ACh, 2 to 3

26 Flecainide, a class I antiarrhythmic drug, inhibits Na(+

27 n, we show synergistic functional effects of flecainide, a proarrhythmic Na+ channel blocker, and oxi

28 The effects of flecainide, a sodium (Na(+))-channel blocker, and d,l-so

29 Flecainide acetate directly suppresses sarcoplasmic reti

30 Our data support a model of flecainide action in which Na(+)-dependent modulation of

31 The mechanism of flecainide action remains controversial.

32 Here we examine whether flecainide administration can similarly reduce axonal de

33 Ajmaline, procainamide, or flecainide administration resulted in ST-segment elevati

34 Flecainide administration significantly reduced the mean

35 masked using sodium channel blockers such as flecainide, ajmaline or procainamide, thus identifying p

36 e has been proposed as a treatment for LQT3, flecainide also evokes "Brugada-like" ST-segment elevati

37 ciate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome elec

38 treatment strategies include beta-blockade, flecainide and ICD implementation--none of which is full

39 ally, comparable outcomes were found between flecainide and labetalol antiarrhythmic effects in vitro

40 Newer options such as flecainide and left cardiac sympathetic denervation are

41 us adverse events did not differ between the flecainide and placebo arms.

42 ias during exercise was compared between the flecainide and placebo arms.

43 ute arrhythmogenesis and its modification by flecainide and quinidine to alterations in DeltaAPD90 in

44 Electrophysiological effects of flecainide and quinidine were compared in Langendorff-pe

45 murine hearts in the presence and absence of flecainide and quinidine, and the extent to which Scn5a+

46 Flecainide and RAD-243 retained their use-dependent bloc

47 scopic current relaxation during exposure to flecainide and RAD-243.

48 After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal s

49 The combination of flecainide and sotalol can safely and effectively contro

50 acy and safety of the combination therapy of flecainide and sotalol for the treatment of refractory s

51 s performed identifying infants who required flecainide and sotalol to control refractory SVT.

52 ced from 307+/-35 to 269+/-27 ms (P<.001) by flecainide and subsequently to 217+/-4 ms (P<.001) with

53 d from 198+/-23 to 182+/-17 ms (P=.005) with flecainide and to 164+/-10 ms (P=.004) with isoprotereno

54 ith WT, DeltaKPQ I(Na) was more sensitive to flecainide, and flecainide preferentially inhibited late

55 iverse drugs including lidocaine, phenytoin, flecainide, and quinidine, suggesting that these drugs i

56 ts alpha/beta-adrenergic blocking activity), flecainide, and riluzole; and suppression of abnormal Ca

57 d the open-channel blockers disopyramide and flecainide, and the lidocaine derivative RAD-243.

58 beta-blockers (propranolol and carvedilol), flecainide, and the neuronal sodium-channel blocker rilu

59 Preliminary results with flecainide appear encouraging.

60 Flecainide applied to either the cytoplasmic or luminal

61 ntly, the synergy between catecholamines and flecainide at depolarized Vm and the shortened APD95 cou

62 for predicting proarrhythmic sensitivity to flecainide based on the identification of specific SCN5A

63 e tested lower dose combination therapy with flecainide, beta-blockade and CaMKII inhibition, our mod

64 utions of the open and inactivated states to flecainide binding and inhibition remain controversial.

65 n on repetitive depolarization suggests that flecainide binding is facilitated by channel opening and

66 se data provide insights into mechanisms for flecainide block and provide a rationale at the cellular

67 Flecainide block of Na(+) current (I(Na)) was investigat

68 4-fold delay in recovery from use-dependent flecainide block.

69 o direct evidence to support the notion that flecainide blocks RyR2 Ca(2+) flux in the physiologicall

70 s as the single dose oral loading regimen of flecainide but was superior to those of quinidine and am

71 Recently, flecainide, but not lidocaine, has been found to correct

72 investigated the state-dependent binding of flecainide by examining its inhibition of rapidly inacti

73 the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants

74 a(+) channel alpha-subunit C-terminus in the flecainide/channel interaction.

75 Flecainide completely prevented CPVT in two human subjec

76 ntials (Vm) ([K+]o=5.4 micromol), 1 micromol flecainide decreased Vmax from 698+/-55 to 610+/-72 V/s

77 In intact antral tissue preparations, flecainide depolarized the membrane potential between sl

78 urrent-clamp conditions, exposure to 4-AP or flecainide depolarized the membrane potential by 7-10 mV

79 Flecainide did not affect Ca(2+) transient amplitude, de

80 Moreover, flecainide did not alter RyR2 channel gating and had neg

81 d actions of the drug at the cellular level, flecainide did not inhibit RyR2-dependent sarcoplasmic r

82 , even at supraphysiological concentrations, flecainide did not inhibit the physiologically relevant,

83 placebo, evidence was strong for ibutilide, flecainide, dofetilide, propafenone, amiodarone, and qui

84 To determine whether flecainide dosed to therapeutic levels and added to beta

85 vant, DG channels are blocked selectively by flecainide (EC(50), WT=11.0 and DG=1.7 micromol/L), but

86 In contrast, flecainide effectively prevented triggered activity indu

87 channel effects are insufficient to explain flecainide efficacy in CPVT.

88 channel effects are insufficient to explain flecainide efficacy in CPVT.

89 kinase II inhibition, or by using Mg(2+) or flecainide eliminated delayed afterdepolarizations and d

90 ndependent trials), and rats received either flecainide (Flec) (30 mg/kg/day) or vehicle (Veh) from t

91 day) for 4 weeks (short-term treatment); or flecainide for 6 months (long-term treatment).

92 The mechanism of therapeutic efficacy of flecainide for catecholaminergic polymorphic ventricular

93 ents crossed over to treatment B (placebo or flecainide) for 3 months, followed by exercise testing.

94 ricular outflow tract, which increased after flecainide from 17.6 cm(2) (12.1-24.2) to 28.5 cm(2) (21

95 s with abnormal electrograms increased after flecainide from 19.0 (17.5-23.6) to 27.3 cm(2) (24.0-31.

96 Flecainide further reduced theta', accentuating this RV

97 With K+ depolarization to Vm=-70 mV, flecainide further reduced Vmax from 306+/-101 to 245+/-

98 Flecainide had lesser effects on core size and reentry f

99 The class IC antiarrhythmia drug flecainide has been shown to depress ventricular ectopy

100 Recently, flecainide has gained considerable interest in CPVT trea

101 Two sodium channel blockers, phenytoin and flecainide, have been reported to protect axons in exper

102 ensitive to low micromolar concentrations of flecainide (IC(50) = 11 microM).

103 ls replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 c

104 nts with genetic arrhythmia syndromes (e.g., flecainide in catecholaminergic polymorphic ventricular

105 been proposed that the clinical efficacy of flecainide in CPVT is because of the combined actions of

106 The principal action of flecainide in CPVT is not via a direct interaction with

107 and the response to the antiarrhythmic agent flecainide in Purkinje cells and ventricular myocytes fr

108 Chloroquine is more effective than flecainide in terminating SAF in isolated sheep hearts b

109 indings demonstrate proarrhythmic effects of flecainide in WT and Scn5a+/- murine hearts that recapit

110 Flecainide increased EGD ratios in WT (at 10 microM) and

111 g of membrane depolarization will potentiate flecainide-induced conduction slowing.

112 the addition of isoproterenol magnified the flecainide-induced reduction of Vmax an additional 24% t

113 depolarized Vm, isoproterenol amplified the flecainide-induced reduction of Vmax and theta2, suggest

114 the frequency of stimulation potentiated the flecainide inhibition (IC(50) = 7.4 microM), which progr

115 Although the flecainide inhibition of Nav1.5 is typically enhanced by

116 age sensitivity and strong dependence of the flecainide inhibition on repetitive depolarization sugge

117 states, which failed to promote significant flecainide inhibition.

118 Flecainide is a Class I antiarrhythmic drug and a potent

119 who develops a Brugada electrocardiogram on flecainide is diagnosed with "asymptomatic BrS" and coul

120 u = 7.4 +/- 0.1 s) channels, suggesting that flecainide is trapped and not tightly bound within the p

121 revious drug therapy, duration of treatment, flecainide levels and corrected QT intervals were record

122 shown that the class IC agents encainide and flecainide may increase the energy requirements for paci

123 cted superior therapeutic efficacy than with flecainide monotherapy.

124 tudy is to identify inhibitory mechanisms of flecainide on RyR2.

125 Patients received oral flecainide or placebo twice daily, with the dosage guide

126 atients were then randomized to treatment A (flecainide or placebo) for 3 months, followed by exercis

127 ing incremental pacing, before and following flecainide or quinidine challenge.

128 Flecainide or quinidine decreased the pacing rates at wh

129 drugs, with carvedilol and JTV-519 (but not flecainide or riluzole) acting primarily through sarcopl

130 t two antiarrhythmic agents including either flecainide or sotalol as single agents before initiating

131 omized clinical trial of patients with CPVT, flecainide plus beta-blocker significantly reduced ventr

132 At diastolic cytoplasmic [Ca(2+)] (100 nM), flecainide possesses an additional inhibitory mechanism

133 I(Na) was more sensitive to flecainide, and flecainide preferentially inhibited late I(Na) (mean cur

134 Flecainide prevented catecholamine-induced sustained ven

135 Flecainide prevented initiation of VT in 13 out of 16 ar

136 We discovered that flecainide prevents arrhythmias in a mouse model of CPVT

137 Flecainide prevents catecholaminergic polymorphic ventri

138 To elucidate the potential mechanism for the flecainide proarrhythmia observed in CAST, the voltage d

139 Flecainide produced a time-dependent decay in the curren

140 he tibial nerve of EAN animals revealed that flecainide provided significant protection against axona

141 The data indicate that flecainide rapidly gains access to its binding site when

142 During pacing (n=11), flecainide reversibly reduced conduction velocity ( appr

143 holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c(+/-) a

144 activation and intermediate inactivation) to flecainide sensitivity in patients carrying LQT3 and Bru

145 At hyperpolarized voltages, flecainide slowed the recovery of both the rapidly inact

146 f epicardial and endocardial Ito channels to flecainide, suggesting that the current is produced by t

147 c modulation of impulse propagation in eight flecainide-superfused canine Purkinje fibers was examine

148 The addition of 1 micromol isoproterenol to flecainide-superfused fibers at physiological Vm increas

149 Flecainide testing was performed at each follow-up visit

150 ude that DeltaKPQ interacts differently with flecainide than with WT, leading to increased block and

151 Flecainide then increased arrhythmic tendency and EGD ra

152 Our simulations suggest that flecainide therapeutic efficacy in CPVT is unlikely to d

153 It is possible for flecainide to directly affect the cardiac ryanodine rece

154 The binding of flecainide to open channels was further investigated in

155 C(50), WT=894 and DG=205 micromol/L) but not flecainide tonic block in a concentration range that is

156 0% of the normal number of axons survived in flecainide-treated rats compared with 62.8% in vehicle-t

157 e (10 microM) prevented VT in six out of six flecainide-treated WT and 13 out of the 16 arrhythmogeni

158 VT occurred in 11 out of 16 (10 microM) flecainide-treated WT and nine out of the 13 initially n

159 ol-induced arrhythmias that are prevented by flecainide treatment.

160 onse on expressed channels; (2) suggest that flecainide use-dependent block of DG channels underlies

161 Flecainide was also potent in suppressing microglial act

162 The effect of flecainide was not abolished by inhibiting enteric neuro

163 ollow-up data from 242 patients showing that flecainide was superior to no treatment (Kaplan-Meier su

164 Flecainide was used in 24% and left cardiac sympathetic

165 on of spontaneous Ca(2+) release events with flecainide, whereas in RyR2(R4496C/+) mice, the Purkinje

166 were substantially reduced by amiodarone or flecainide, which are drugs that have sodium channel-blo

167 For quinidine and flecainide, which bind preferentially to the open Na+ ch

168 the classical sodium channel blocking agent, flecainide, which has no recognized monoamine oxidase B

169 Flecainide, which preferentially inhibits mutation-alter

170 Applying flecainide while briefly depolarizing from a relatively

171 4-aminopyridine (4-AP) and was inhibited by flecainide, with an IC(50) of 35 microM.

172 he activation or the inactivation gate traps flecainide within the pore resulting in the slow recover