ライフサイエンスコーパス: amantadine

1 activity is inhibited by the antiviral drug amantadine.

2 e absence and presence of the antiviral drug amantadine.

3 ssible viruses in the presence or absence of amantadine.

4 pH, cholesterol, and the antiinfluenza drug Amantadine.

5 otetramers that bind the anti-influenza drug amantadine.

6 otein is not inhibited by the antiviral drug amantadine.

7 f the largest chemical shift perturbation by amantadine.

8 ion channel that was partially inhibited by amantadine.

9 itro genetic barrier to drug resistance than amantadine.

10 ng resistance of influenza A viruses against amantadine.

11 nce and absence of the channel-blocking drug amantadine.

12 target for the action of the antiviral drug amantadine.

13 hain are more constrained in the presence of amantadine.

14 mutant, S31N, in the presence and absence of amantadine.

15 signed to inhibit viruses with resistance to amantadine.

16 ted with ketamine, midazolam, ribavirin, and amantadine.

17 y of M2TM in the absence and the presence of amantadine.

18 r virus functioning and a target of the drug amantadine.

19 that retain the ability to bind to the drug amantadine.

20 of influenza virus grown in the presence of amantadine.

21 generated that appears adequate for binding amantadine.

22 ole determinant of resistance of A/WSN/33 to amantadine.

23 a double-blind, placebo-controlled trial of amantadine.

24 or the observed inhibition of proton flux by amantadine.

25 n channels, which are the target of the drug amantadine.

26 in, clathrin adaptor AP-2, and hsc70, and 2) amantadine.

27 e ammonium group of the anti-viral compound, amantadine.

28 iral function and are the target of the drug amantadine.

29 M2-V27S, which is resistant to the inhibitor amantadine.

30 2,500-fold more effective than ribavirin or amantadine.

31 that can be inhibited by the antiviral drug amantadine.

32 743 resistant but is reversibly inhibited by amantadine.

33 olidine derivatives designed as analogues of amantadine.

34 associated with resistance to the antiviral amantadine.

35 es and shows greatly decreased inhibition by amantadine.

36 odulates the ability of the TM helix to bind amantadine.

37 nfected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant h

38 nd 50 mg, respectively) four times a day and amantadine (100 mg) three times a day without adequate i

39 ystem to receive either oseltamivir (75 mg), amantadine (100 mg), and ribavirin (600 mg) combination

40 vs 75 [7], p<0.0001) as was block by 100 muM amantadine (18% [4] vs 44 [12], p<0.0001).

41 When amantadine (20 mg/kg) or budipine (5 mg/kg) was co-admin

42 crog/kg per week), ribavirin (800 mg/d) plus amantadine (200 mg/d), or PEG interferon alpha 2b (1.0 m

43 g increases in AADC were noted with 40 mg/kg amantadine (3.8-fold for CS, 9.0-fold for SN), 40 mg/kg

44 Acutely, amantadine (40 mg/kg) or budipine (10 mg/kg) did not sig

45 udipine (10 mg/kg), memantine (40 mg/kg) and amantadine (40 mg/kg) strongly increased DDC, whilst not

46 Amantadine, a drug known to inhibit influenza A viral ma

47 Amantadine accelerated the pace of functional recovery d

48 These data indicate that amantadine affects the M2 proton channel mainly by chang

49 Amantadine also reduces the conformational heterogeneity

50 model suggests that Ser31 may interact with amantadine amine via hydrogen bonding.

51 his end, we have investigated the binding of amantadine (Amt) to the wild type (wt) M2 channel and it

52 he primary binding site for the antiflu drug amantadine (AMT), probably because that domain is relati

53 The interactions of (15)N-labeled amantadine, an antiinfluenza A drug, with DMPC bilayers

54 )]undecane scaffold designed as analogues of amantadine, an inhibitor of the M2 proton channel of inf

55 Amantadine, an N-methyl-D-aspartate antagonist, is so fa

56 While most of the research on novel amantadine analogues has revolved around the synthesis o

57 ients given moderate doses (2000-4000 mg) of amantadine and 2.84 times higher in the subgroup of pati

58 The effects of amantadine and a related analogue, rimantadine, on viral

59 ional differences between two M2 inhibitors, amantadine and BL-1743, are distinguished by the microph

60 Amantadine and budipine did not significantly alter extr

61 ave studied the effects of administration of amantadine and budipine with the antidepressants reboxet

62 mutation (S31N) with improved efficacy over amantadine and HMA (IC50 = 0.6 microM and 4.4 microM, re

63 2 channel activity is inhibited by the drugs amantadine and its methyl derivative rimantadine.

64 The ability of amantadine and memantine to potentiate the antiparkinson

65 drugs with wide therapeutic utility, such as amantadine and memantine.

66 We found marginal efficacy for amantadine and mood stabilizers, but found no increased

67 The receptor-mediated endocytosis inhibitors amantadine and phenylarsine oxide inhibited the binding

68 patients with chronic HCV infection received amantadine and ribavirin, combined with 6 weeks of high-

69 is inhibited by aminoadamantyl drugs such as amantadine and rimantadine (Rmt).

70 The M2 ion channel inhibitors amantadine and rimantadine are effective for prophylaxis

71 rug-protein cross peaks, which indicate that amantadine and rimantadine bind to the pore in the same

72 s prophylaxis against influenza in families, amantadine and rimantadine have had inconsistent effecti

73 In conclusion, amantadine and rimantadine have no direct and specific i

74 xterior rather than to His37, in contrast to amantadine and rimantadine in the wild-type channel, sug

75 Amantadine and rimantadine share features that would mak

76 Unlike amantadine and rimantadine that target the M2 protein of

77 Adamantanes (amantadine and rimantadine) are one of the two classes o

78 eviously available agents, the M2 inhibitors amantadine and rimantadine, could only be used to treat

79 The adamantanes, amantadine and rimantadine, have been used as first-choi

80 Anti-influenza drugs, amantadine and rimantadine, targeting the M2 channel fro

81 The activity of p7 can be inhibited by amantadine and rimantadine, which are potent blockers of

82 nhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bin

83 N1, tend to be sensitive to antiviral drugs, amantadine and rimantadine, while the S31N mutant viruse

84 uenza A is the target of the antiviral drugs amantadine and rimantadine, whose effectiveness has been

85 rus is a target for the anti-influenza drugs amantadine and rimantadine, whose effectiveness was dimi

86 (A/M2) is the target of the antiviral drugs amantadine and rimantadine, whose use has been discontin

87 that are known to confer resistance to both amantadine and rimantadine.

88 and in vivo by the M2 ion-channel inhibitors amantadine and rimantadine.

89 M2 proton channel that confer resistance to amantadine and rimantadine.

90 oton channel targeted by the antiviral drugs amantadine and rimantadine.

91 lop in vivo resistance of influenza virus to amantadine and to zanamivir, by use of the ferret model

92 channel is the target of the antiviral drug amantadine (and its methyl derivative rimantadine), wher

93 y (+)MK-801, (-)MK-801, ketamine, memantine, amantadine, and dextrorphan.

94 ase 2 trial of a combination of oseltamivir, amantadine, and ribavirin versus oseltamivir monotherapy

95 Recently, a new family of compounds based on amantadine- and aryl-substituted isoxazole were discover

96 onoamine oxidase type B inhibitors [MAOBIs], amantadine, anticholinergics, beta-blockers, or dopamine

97 The tetramerization and binding of amantadine are more favorable at elevated pH, with a pK(

98 was monitored in the absence and presence of amantadine as a function of pH.

99 ntrolled clinical trial suggested a role for amantadine as a treatment for pathological gambling in p

100 agents (ammonium chloride, chloroquine, and amantadine), as well as energy depletion, prevented BDV

101 This amantadine association remained after controlling for co

102 docking calculations, the open channel binds amantadine at the more favorable internal site, in good

103 Moreover, binding of the antiviral drug, amantadine, at the N-terminal pore at low pH did not con

104 was blocked by the M2 ion channel inhibitor, amantadine); b) had current-voltage relationships that s

105 gnificant microsecond-time scale motion, and amantadine binding alters the motional rates, causing li

106 Our results confirm that amantadine binding inhibits current flow through NMDA re

107 ucture of the M2 protein and its change upon amantadine binding is crucial for designing antiviral dr

108 hanism for the pH-dependent association, and amantadine binding of M2, based on studies of a peptide

109 All of the mutations destabilized amantadine binding or were isoenergetic.

110 eptide than the apo peptide, indicating that amantadine binding reduces the conformational heterogene

111 olid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-contain

112 t spot is an internal cavity overlapping the amantadine binding site seen in the x-ray structure.

113 The influence of amantadine binding through comparative cross polarizatio

114 t that 9: binds at site(s) that overlap with amantadine binding.

115 esults are consistent with a location of the amantadine-binding site inside the channel pore.

116 ed size, polarity, and dynamic nature of its amantadine-binding site.

117 how by solid-state NMR spectroscopy that two amantadine-binding sites exist in M2 in phospholipid bil

118 mpounds, consistent with the conclusion that amantadine binds inside the channel pore.

119 Amantadine block was reduced at pH 5.4.

120 ported by our finding that the M2 inhibitor, amantadine, blocked its activity in vitro.

121 onstruct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel.

122 lution) in the channel pore, consistent with amantadine blocking the pore of the channel.

123 Amantadine blocks this channel, thus inhibiting viral re

124 A structural model of the amantadine bound state of M2TM was generated using a nov

125 rge to small residue changes destabilize the amantadine bound tetramer whereas mutations to side-chai

126 d the overall free energy of assembly of the amantadine bound tetramer.

127 The amantadine-bound form exhibited a single peak approximat

128 sion angles cause a kink of 5 degrees in the amantadine-bound helix.

129 closed state, and the slowest in the high-pH amantadine-bound state.

130 domain of the protein M2TMP in the apo- and amantadine-bound states in lipid bilayers.

131 Treatment with amantadine, bromocriptine, and lorazepam was unsuccessfu

132 of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtain

133 bited by the ion channel blockers barium and amantadine but not by cesium.

134 other described channel-blocking molecules, amantadine causes the channel gate of NMDA receptors to

135 Finally, amantadine causes the helical segment N-terminal to G34

136 AM2 is inhibited by the amantadine class of antiviral drugs, whereas BM2 has no

137 on-selective channel that is targeted by the amantadine class of antiviral drugs.

138 meric proton channel that is targeted by the amantadine class of antiviral drugs.

139 protonation equilibrium model, suggest that amantadine competes with protons for binding to the depr

140 Similarly, pretreatment of target cells with amantadine, concanamycin A, concanamycin B, chloroquine,

141 linically tolerated NMDA antagonists such as amantadine could reduce the delay in therapeutic onset o

142 al testing, we discovered benzyl-substituted amantadine derivatives with activity against both S31N a

143 Quantification of the protein-amantadine distances resulted in a 0.3 A-resolution stru

144 valuate the efficacy and safety of ADS-5102 (amantadine) extended-release 274-mg capsules for treatme

145 Compound 9: competes with amantadine for M2 inhibition, and molecular docking simu

146 ompared with the first pK(a) of histidine in amantadine-free M(2)-TMD.

147 The rate of improvement in the amantadine group slowed during the 2 weeks after treatme

148 od, recovery was significantly faster in the amantadine group than in the placebo group, as measured

149 Amantadine has been used for decades as an inhibitor of

150 Inhibition of p7-mediated currents by amantadine, however, exhibited significant, genotype-spe

151 Amantadine hydrochloride is one of the most commonly pre

152 than an order of magnitude more potent than amantadine (IC(50) = 16 microM).

153 influenza viruses is comparable with that of amantadine in inhibiting WT influenza virus.

154 The study examined the effectiveness of amantadine in reducing cocaine withdrawal symptoms and i

155 ed electron densities attributed to a single amantadine in the amino-terminal half of the pore, indic

156 ical trials, is needed to assess the role of amantadine in the development and treatment of ICDs in P

157 hors evaluated the efficacy of buspirone and amantadine in the treatment of sexual dysfunction associ

158 ing an unvaccinated 75-year-old patient with amantadine increased life expectancy by 0.0014 QALY at a

159 Amantadine increases the risk of corneal edema in a dose

160 ence of the M2-specific ion channel blocker, amantadine, indicating that the Golgi transport delay is

161 Consistently, Cu(II) and amantadine induce distinct conformational changes at sev

162 fluenza A virus M2 protein is a pH-gated and amantadine-inhibited proton channel important for the vi

163 However, BL-1743 inhibition and amantadine inhibition have similar properties.

164 In contrast, amantadine inhibition is irreversible within the time fr

165 These results give insights into the lack of amantadine inhibition of BM2 and reveal structural diver

166 We describe here the molecular mechanism of amantadine inhibition.

167 Amantadine inhibits the M2 proton channel of influenza A

168 The anti-influenza drug, amantadine, inhibits the channel activity through bindin

169 annels between amantadine-sensitive A/M2 and amantadine-insensitive BM2 designed to define the drug-b

170 n the pore is a probable explanation for the amantadine insensitivity of the BM2 protein and suggests

171 l backbone, while the hydrocarbon portion of amantadine interacts with the glycerol backbone and much

172 for the N-terminal residues, indicating that amantadine is bound to the pore lumen between Gly(34) an

173 elusive, and the mechanism of inhibition by amantadine is controversial.

174 Amantadine is known to block the M2 proton channel of th

175 al results demonstrate that the long axis of amantadine is on average parallel to the bilayer normal,

176 xation and by the MD simulation showing that amantadine is within the interfacial region and that the

177 The high-affinity site, occupied by a single amantadine, is located in the N-terminal channel lumen,

178 Both tetramerization and the binding of amantadine lead to increases in the magnitude of the ell

179 Binding amantadine lowers the His(37) pK(a) values by approximat

180 Amantadine may be an effective treatment for cocaine-dep

181 operties suggests a novel mechanism by which amantadine may inhibit proton conductance.

182 Preliminary studies have suggested that amantadine may promote functional recovery.

183 Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated

184 The x-ray structure shows a single amantadine molecule in the middle of the channel, wherea

185 eas the crystal structure indicates a single amantadine molecule in the pore of the channel, the NMR

186 -week treatment trial with buspirone (N=19), amantadine (N=18), or placebo (N=20).

187 ent sensitive to the M(2)-specific inhibitor amantadine) of the cytoplasmic tail truncation mutants e

188 We have investigated the effect of amantadine on the growth of four influenza viruses: A/WS

189 e influenza virus inhibitors oseltamivir and amantadine on the kinetics of in vivo infection progress

190 . falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C1

191 When amantadine or budipine was administered 30 min before th

192 rents with 3- to 6-fold greater potency than amantadine or HMA (IC50 = 0.2 vs. 0.6 and 1.3 microM, re

193 Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for

194 peripheral and pore-forming helices to which amantadine or rimantadine binds, and compound binding sp

195 conductance of M2 using the anti-viral drug amantadine or rimantadine inhibits viral replication.

196 06) but not correlated with use of levodopa, amantadine, or anticholinergic drugs.

197 These results indicate that amantadine physically occludes the M2 channel, thus pavi

198 Binding of amantadine physically occludes the pore, and might also

199 with siRNA, or inhibition of its activity by amantadine, prevented the decrease in CFTR expression an

200 eutral conditions, external addition of 1 mM amantadine produced a reduction in flux consistent with

201 Compared with amantadine, rapid diagnostic testing followed by treatme

202 all known amino acid changes which result in amantadine resistance also confer BL-1743 resistance.

203 domain of the protein has caused widespread amantadine resistance in most of the currently circulati

204 New insights on the amantadine resistance mechanism of the V27A mutant were

205 ons on reversal potential, ion currents, and amantadine resistance were measured.

206 s amantadine sensitive, whereas A/WSN/33 was amantadine resistant, indicating that the M2 residue N31

207 luenza viruses resistant to BL-1743 are also amantadine resistant.

208 ion of the wild-type (WT) M2 channel and the amantadine-resistant A/M2-S31N and A/M2-V27A mutant ion

209 Of note, two of the compounds inhibited the amantadine-resistant A/M2-V27A and A/M2-L26F mutant ion

210 The technique was also used to detect amantadine-resistant isolates.

211 S31N is the predominant and amantadine-resistant M2 mutant, present in almost all of

212 These results are consistent with the amantadine-resistant mutant being dominant and the oligo

213 ively block the M2 proton channel, including amantadine-resistant mutant channels.

214 drugs that target the His37 site to inhibit amantadine-resistant mutant M2 proteins.

215 In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and a

216 Although a large number of functional amantadine-resistant mutants of A/M2 have been observed

217 that target this binding site in a number of amantadine-resistant mutants.

218 ermany/2/81 (H1N1) by using the frequency of amantadine-resistant mutants.

219 Amantadine-resistant mutations thus may arise from bindi

220 ering the design of novel drugs that inhibit amantadine-resistant strains of influenza A virus.

221 ite is lined by residues that are mutated in amantadine-resistant viruses.

222 nel lumen, surrounded by residues mutated in amantadine-resistant viruses.

223 ions in the M2 protein that render the virus amantadine-resistant.

224 The binding of the channel inhibitor, amantadine, results in no change in the backbone structu

225 Amantadine, rimantadine, and the newly available drugs z

226 four currently approved antiviral agents are amantadine, rimantadine, zanamivir [Relenza, Glaxo Wellc

227 as one CH2 group to the methyl adduct of the amantadine/rimantadine analogue, 2-methyl-2-aminoadamant

228 en together our functional data suggest that amantadine/rimantadine binding outside of the channel po

229 These functional data suggest that the amantadine/rimantadine binding site identified on the ou

230 esidues 24-36 of the A/M2 TM domain show 85% amantadine/rimantadine sensitivity and specific activity

231 Amantadine's influence on the His(37) chemical propertie

232 hat inhibit S31N with potencies greater than amantadine's potency against WT M2.

233 Piracetam, amantadine, selegiline, olanzapine, quetiapine, risperid

234 N31S-M2WSN was amantadine sensitive, whereas A/WSN/33 was amantadine re

235 The current amplitude is amantadine sensitive.

236 We have generated chimeric channels between amantadine-sensitive A/M2 and amantadine-insensitive BM2

237 e hydrochloride)-resistant human viruses and amantadine-sensitive avian strains.

238 wn to form acid-activated, proton-selective, amantadine-sensitive channels.

239 Na- was replaced by NH4+ or Li+); c) had an amantadine-sensitive influx of Rb+.

240 The amantadine-sensitive ion channel activity of influenza A

241 -N-carbamimidoylnicotinamide ( 9: ) inhibits amantadine-sensitive M2 currents with 3- to 6-fold great

242 nd to transport protons into liposomes in an amantadine-sensitive manner.

243 o the cytoplasmic membrane and had specific, amantadine-sensitive proton transport activity indisting

244 (TM) domain (roughly residues 22-46) for the amantadine-sensitive proton-channel activity and an amph

245 ion assays, which confirmed the much reduced amantadine sensitivity of genotypes 2a and 3a.

246 o mutant protein subunits was 0.85:0.15, the amantadine sensitivity was reduced to 50% and for a rati

247 Their ion selectivity, amantadine sensitivity, specific activity, and pH-depend

248 mer-tetramer equilibrium, and the binding of amantadine shifts the monomer-tetramer equilibrium towar

249 ts of (13)C-labeled protein and (2)H-labeled amantadine showed that in 1,2-dimyristoyl-sn-glycero-3-p

250 ompetitive NMDA receptor antagonists such as amantadine showing synergy with conventional antidepress

251 Compared to amantadine, spiro-piperidine 9 (1) induces a more homoge

252 Analyses of the amantadine subgroup by cumulative dose revealed that the

253 r corneal edema was 1.79 times higher in the amantadine subgroup.

254 who received placebo, subjects who received amantadine submitted significantly more benzoylecgonine-

255 Binding of the antiviral drug amantadine suppressed both proton exchange and ring moti

256 em side effects, which occur more often with amantadine than rimantadine, and potential drug interact

257 o BL-1743 and only 10-fold more resistant to amantadine than the wild-type virus.

258 was further subgrouped by use and non-use of amantadine, the hazard ratio for corneal edema was 1.79

259 n transfer indicates that, in the absence of amantadine, the initial spin diffusion rate mainly depen

260 anging from 2483 dollars per QALY saved with amantadine to 70,300 dollars per QALY saved with oseltam

261 selective serotonin reuptake inhibitors and amantadine to assist motor recovery poststroke and traum

262 of the tetramer, we measured the binding of amantadine to the resting state of the channel, and exam

263 While the amantadine-treated women did report significantly greate

264 on in all cell types, whereas, surprisingly, amantadine treatment more efficiently blocked infection

265 Empirical amantadine treatment offers a low-cost alternative if pa

266 e the risk between patients with and without amantadine treatment.

267 ICDs) in PD, amantadine use (n = 728), vs no amantadine use (n = 2,357), was positively associated wi

268 y of impulse control disorders (ICDs) in PD, amantadine use (n = 728), vs no amantadine use (n = 2,35

269 Similar to the situation in humans, amantadine use in ferrets rapidly produces antiviral res

270 remained after controlling for covariates of amantadine use, including both dopamine agonist use and

271 t the start of treatment, those who received amantadine used significantly less cocaine during the tr

272 cle that are inhibited by the antiviral drug amantadine: virus uncoating in endosomes and M2 protein-

273 The growth of influenza viruses inhibited by amantadine was compared to the growth of an M2-del(29-31

274 The localization of amantadine was determined by paramagnetic relaxation and

275 In one small study, amantadine was found to produce some response in patient

276 influenza virus A/LosAngeles/1/87 (H3N2) to amantadine was generated within 6 days, during a single

277 ecently, little advance in its control since amantadine was licensed almost 40 years ago.

278 Neither buspirone nor amantadine was more effective than placebo in ameliorati

279 ing antisera against the human virus HAs and amantadine, we selected reassortants containing the huma

280 wn to bind inside the A/M2 channel pore, and amantadine were exploited to demonstrate competition bet

281 he D44A channel was found to be sensitive to amantadine when measured by electrophysiological recordi

282 Amantadine, which blocks proton conductance by binding i

283 Amantadine, which blocks the budding of clathrin-coated

284 parallels the pH dependence of inhibition by amantadine, which has previously been ascribed to proton

285 rom the binding site of the hydrophobic drug amantadine, which is about 10 A N-terminal to His37.

286 so demonstrated that the anti-influenza drug amantadine, which targets the M2 proton channel, suppres