ライフサイエンスコーパス: amantadine

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

2 activity is inhibited by the antiviral drug amantadine.

3 e absence and presence of the antiviral drug amantadine.

4 ssible viruses in the presence or absence of 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 ng resistance of influenza A viruses against amantadine.

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

11 target for the action of the antiviral drug amantadine.

12 hain are more constrained in the presence of amantadine.

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

14 annel blockers, but not the AM2 WT inhibitor amantadine.

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

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

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

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

19 of influenza virus grown in the presence of amantadine.

20 generated that appears adequate for binding amantadine.

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

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

23 or the observed inhibition of proton flux by amantadine.

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

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

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

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

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

29 associated with resistance to the antiviral amantadine.

30 pH, cholesterol, and the antiinfluenza drug Amantadine.

31 itro genetic barrier to drug resistance than amantadine.

32 signed to inhibit viruses with resistance to amantadine.

33 olidine derivatives designed as analogues of amantadine.

34 es and shows greatly decreased inhibition by amantadine.

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

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

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

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

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

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

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

42 .2-43.1) with placebo, 41.3 (38.8-43.7) with amantadine, 39.0 (36.6-41.4) with modafinil, and 38.6 (3

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

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

45 cipants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40

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

47 scious state based on a clinical trial using amantadine, a weak dopamine transporter blocker.

48 Amantadine accelerated the pace of functional recovery d

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

50 Amantadine also reduces the conformational heterogeneity

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

52 uenza A M2 channel renders it insensitive to amantadine (AMT) and rimantadine (RMT) block, but it is

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

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

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

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

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

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

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

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

61 Amantadine and budipine did not significantly alter extr

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

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

64 2 channel activity is inhibited by the drugs amantadine and its methyl derivative rimantadine.

65 The ability of amantadine and memantine to potentiate the antiparkinson

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

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

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

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

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

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

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

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

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

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

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 oton channel targeted by the antiviral drugs amantadine and rimantadine.

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

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

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

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

92 However, only two studies on amantadine and transcranial direct current stimulation p

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

94 monary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requir

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

96 %) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to

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

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

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

100 Methylphenidate, modafinil, and amantadine are commonly prescribed medications for allev

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

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

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

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

105 This amantadine association remained after controlling for co

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

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

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

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

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

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

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

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

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

115 with the exception of water molecules in the amantadine binding site not included in the Rosetta desi

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

117 The influence of amantadine binding through comparative cross polarizatio

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

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

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

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

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

123 s, in contrast to the single phase found for amantadine block of wild-type M2.

124 Amantadine block was reduced at pH 5.4.

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

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

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

128 Amantadine blocks this channel, thus inhibiting viral re

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

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

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

132 The amantadine-bound form exhibited a single peak approximat

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

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

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

136 Treatment with amantadine, bromocriptine, and lorazepam was unsuccessfu

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

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

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

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

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

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

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

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

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

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

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

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

149 In so doing, amantadine enhances dendritic integration of excitatory

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

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

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

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

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

155 Amantadine has been used for decades as an inhibitor of

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

157 Amantadine hydrochloride is one of the most commonly pre

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

159 31N/L46P, and equal binding free energies of amantadine in complex with AM2 WT and AM2 L46P.

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

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

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

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

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

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

166 Amantadine increases the risk of corneal edema in a dose

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

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

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

170 We describe here the molecular mechanism of amantadine inhibition.

171 M2 WT, the channel remained sensitive toward amantadine inhibition.

172 Amantadine inhibits the M2 proton channel of influenza A

173 dministration-approved influenza A antiviral amantadine inhibits the wild-type (WT) AM2 channel but n

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

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

176 ge-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current bloc

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

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

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

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

181 Amantadine is currently the only drug proven to alleviat

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

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

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

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

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

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

188 Amantadine may be an effective treatment for cocaine-dep

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

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

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

192 equence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 3

193 trials, as patients currently refractory to amantadine might benefit from them.

194 Amantadine, modafinil, and methylphenidate were not supe

195 tudy do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatm

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

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

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

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

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

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

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

203 When amantadine or budipine was administered 30 min before th

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

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

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

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

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

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

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

211 stration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequ

212 at therapeutically relevant concentrations, amantadine preferentially blocks inward-rectifying K+ ch

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

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

215 Compared with amantadine, rapid diagnostic testing followed by treatme

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

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

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

219 Furthermore, the prevalence of amantadine resistance-conferring M2 mutations increased

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

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

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

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

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

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

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

227 also show that the complexes block the G34E amantadine-resistant mutant despite some crowding in the

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

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

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

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

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

233 Amantadine-resistant mutations thus may arise from bindi

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

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

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

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

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

239 Amantadine, rimantadine, and the newly available drugs z

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

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

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

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

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

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

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

247 Piracetam, amantadine, selegiline, olanzapine, quetiapine, risperid

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

249 The current amplitude is amantadine sensitive.

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

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

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

253 The amantadine-sensitive ion channel activity of influenza A

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

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

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

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

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

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

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

261 the methylphenidate, modafinil, placebo, and amantadine sequence.

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

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

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

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

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

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

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

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

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

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

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

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

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

275 While the amantadine-treated women did report significantly greate

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

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

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

279 Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to

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

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

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

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

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

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

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

287 The localization of amantadine was determined by paramagnetic relaxation and

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

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

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

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

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

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

294 Amantadine, which blocks proton conductance by binding i

295 Amantadine, which blocks the budding of clathrin-coated

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

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

298 residues 26-34, but not of AM2 WT inhibitor amantadine, which spans residues 31-34.

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

300 binds the C(3) symmetric small molecule drug amantadine with each protein monomer making identical in