ライフサイエンスコーパス: fenfluramine

1 logic challenge of the serotonin system (d,l-fenfluramine).

2 se of dexfenfluramine and 6 after the use of fenfluramine.

3 inhibitor, paroxetine, or a releasing drug, fenfluramine.

4 significantly blunted prolactin response to fenfluramine.

5 order by measuring the prolactin response to fenfluramine.

6 the anorexia produced by an alternate agent, fenfluramine.

7 tinuation of dexfenfluramine and phentermine/fenfluramine.

8 ite-suppressant drugs, including phentermine-fenfluramine.

9 e long-term consequences of prolonged use of fenfluramines.

10 s to 4.7 seizures per 28 days), 42.3% in the fenfluramine 0.2 mg/kg group (from median 17.5 seizures

11 le) were randomly assigned to receive either fenfluramine 0.2 mg/kg per day (39), fenfluramine 0.7 mg

12 d with placebo (95% CI 47.7-72.8, p<0.0001); fenfluramine 0.2 mg/kg per day showed a 32.4% reduction

13 response system in a 1:1:1 ratio to placebo, fenfluramine 0.2 mg/kg per day, or fenfluramine 0.7 mg/k

14 uction in seizure frequency was 74.9% in the fenfluramine 0.7 mg/kg group (from median 20.7 seizures

15 either fenfluramine 0.2 mg/kg per day (39), fenfluramine 0.7 mg/kg per day (40) or placebo (40).

16 tudy met its primary efficacy endpoint, with fenfluramine 0.7 mg/kg per day showing a 62.3% greater r

17 placebo, fenfluramine 0.2 mg/kg per day, or fenfluramine 0.7 mg/kg per day, added to existing antiep

18 Administration of the drugs in combination (fenfluramine 1 mg/kg and phentermine 2 mg/kg) amplified

19 Acute or chronic administration of fenfluramine (1 mg/kg, i.p.) did not significantly chang

20 of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-

21 d,l-Fenfluramine (10 mg/kg) evoked an increase in extracellu

22 The 5-HT-releasing agent, fenfluramine (10 microM), and the Na-releasing agent, am

23 ol animals and those pretreated with MDMA or fenfluramine (10, 15 and 20 mg/kg administered on succes

24 wley rats were trained to discriminate (+/-)-fenfluramine (2 mg/kg ip) from saline using a 2-lever, w

25 uncommon (dexfenfluramine, 2.3%; phentermine/fenfluramine, 2.4%, and untreated, 3.3%, when adjusted f

26 A higher dose of d,l-fenfluramine (20 mg/kg) produced a significantly greater

27 subjects (dexfenfluramine, 9.0%; phentermine/fenfluramine, 4.0%; and untreated, 8.4%); and following

28 ed with propofol and administered a bolus of fenfluramine (5 mg/kg).

29 tonin-releasing agent and reuptake inhibitor fenfluramine (60 mg p.o.) and 3 hours afterward.

30 D-Fenfluramine, a putative serotonin releaser and reuptake

31 Fenfluramine, a serotonin releaser and uptake inhibitor,

32 ne and prolactin were elevated 2 hours after fenfluramine administration and remained significantly e

33 uring serotonin axonal markers 2 weeks after fenfluramine administration.

34 This difference was more pronounced after fenfluramine administration.

35 ic activities of the amphetamine derivatives fenfluramine (an appetite suppressant) and 3,4-methylene

36 in (5-HT) transporter (SERT) substrates like fenfluramine and 3,4-methylenedioxymethamphetamine cause

37 The association of fenfluramine and certain other anorexic agents with seri

38 , 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of bra

39 association between the dietary suppressants fenfluramine and dexfenfluramine and valvular heart dise

40 suggested that up to 30% to 38% of users of fenfluramine and dexfenfluramine had valvular disease, t

41 Fenfluramine and dexfenfluramine have been demonstrated

42 Fenfluramine and dexfenfluramine were voluntarily withdr

43 erse effects that came to be associated with fenfluramine and dexfenfluramine, leading to their event

44 Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists

45 announcement of the voluntary withdrawal of fenfluramine and dexfenfluramine.

46 fflux of [(3)H]5-HT from synaptosomes, but d-fenfluramine and its bioactive metabolite d-norfenfluram

47 ing other amphetamine-like, anorexic agents: fenfluramine and its d-isomer, dexfenfluramine.

48 ular lesions, we examined the interaction of fenfluramine and its metabolite norfenfluramine with 5-H

49 We also demonstrate that MDMA and MDA, like fenfluramine and its N-deethylated metabolite norfenflur

50 Both fenfluramine and its N-methylated analog, N-methylfenflu

51 h potentially useful clinical activity (e.g. fenfluramine and methylenedioxymethamphetamine).

52 sponses in vitro similar to those induced by fenfluramine and norfenfluramine in vivo (i.e., valvular

53 er of prescriptions in the United States for fenfluramine and phentermine exceeded 18 million.

54 e alone, dexfenfluramine and phentermine, or fenfluramine and phentermine for various periods.

55 Fenfluramine and phentermine have been individually appr

56 t a combination of the appetite suppressants fenfluramine and phentermine is associated with an incre

57 The combination of fenfluramine and phentermine was a widely used obesity t

58 ffects of acute or chronic administration of fenfluramine and phentermine, alone or in combination, o

59 Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or

60 mine, and 26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine.

61 Levels of fenfluramine and prolactin were elevated 2 hours after f

62 otonin neurotoxicity in animals treated with fenfluramines and the evidence linking fenfluramines to

63 We tested the hypothesis that fenfluramine (and other anorexic agents) might increase

64 received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess

65 d to increase the risk of PPH (eg, aminorex, fenfluramine, and chlorphentermine) are 5-HT transporter

66 n the isolated, perfused rat lung, aminorex, fenfluramine, and dexfenfluramine induce a dose-related

67 tch-clamp technique, we found that aminorex, fenfluramine, and dexfenfluramine inhibit potassium curr

68 associated with treatment with phentermine, fenfluramine, and dexfenfluramine is now becoming clarif

69 ne-based anorectic compounds diethylpropion, fenfluramine, and phentermine had no effect on K(ATP) ch

70 liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine.

71 that the discriminative stimulus effects of fenfluramine are centrally mediated by 5-HT(2C)R and to

72 dioxymethamphetamine (MDMA or 'Ecstasy') and fenfluramine, are known to damage 5-HT neurons in the br

73 N-methylation did not change the efficacy of fenfluramine as a serotonin neurotoxin, anorectic agent

74 The occurrence of fenfluramine-associated valvular heart disease (VHD) has

75 On serial echocardiography, fenfluramine-associated valvular regurgitation improved

76 were attenuated by pretreatment with MDMA or fenfluramine at both drug-test intervals.

77 Fenfluramine binds weakly to 5-HT(2A), 5-HT(2B), and 5-H

78 ne (10 microM), attenuated the inhibition of fenfluramine but failed to antagonize the effects of exo

79 This study indicates fenfluramine can produce neurotoxicity in rats that disp

80 Fenfluramine causes the release of serotonin proportiona

81 acetic acid, and the prolactin response to d-fenfluramine challenge (PRL[d-FEN]) as central indices o

82 ely correlated with prolactin responses to d-fenfluramine challenge but not with lumbar CSF 5-HIAA co

83 n aggression and the prolactin response to d-fenfluramine challenge in human subjects.

84 The authors applied a dl-fenfluramine challenge method to study metabolic respons

85 t of central serotonergic activity using the fenfluramine challenge procedure.

86 patients with depression (N=162) by using a fenfluramine challenge test and/or measurement of CSF le

87 ly correlated with the prolactin response to fenfluramine challenge.

88 ions and with their prolactin responses to d-fenfluramine challenge.

89 his trial showed that, in patients with LGS, fenfluramine compared with placebo provided a significan

90 Fenfluramine could be an important new treatment option

91 s the blood-brain barrier, did not alter the fenfluramine cue.

92 D-Fenfluramine (D-Fen) increases serotonin (5-HT) content

93 D-fenfluramine (d-FEN) was once widely prescribed and was

94 the pharmacology of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazi

95 Appetite suppressants fenfluramine, dexfenfluramine, and phentermine have been

96 ern has been raised that the d-enantiomer of fenfluramine, dexfenfluramine, may also cause this probl

97 medial parabrachial nucleus (PBN) enhanced d-fenfluramine (DFEN)-induced anorexia; a finding that sug

98 In Experiment 2, the influence of D-fenfluramine (DFEN; 0, 0.5, 1.0, or 2.0 mg/kg) on depriv

99 agonist SB 206553 completely antagonized the fenfluramine discrimination a well as the full substitut

100 measuring fenfluramine-induced anorexia and fenfluramine discrimination.

101 ing, only rats exposed to fenfluramine and d-fenfluramine display depletion of brain 5-HT.

102 We gave male rats once-daily dl-fenfluramine (dl-FEN, 5 mg/kg, i.p.) injections for 15 d

103 unknown significance in BMPR2 in IPAH/HPAH, fenfluramine exposure, and PAH associated with congenita

104 e) or release 5-HT and block its reuptake (D-fenfluramine), failed to enhance motor function.

105 Fenfluramine (FEN) (12.5 mg/kg x 4; injections made hour

106 Repeated administration of D,L-fenfluramine (FEN) is known to cause prolonged depletion

107 d 5HT-related agents, such as the anorexogen fenfluramine (Fen), have been associated with heart valv

108 ressant action of the indirect 5-HT agonists fenfluramine (FEN; 0.63-2.5 mg/kg) and fluoxetine (FLU;

109 The positive control drugs were (+/-)-fenfluramine; (+)-fenfluramine; (-)-fenfluramine; its me

110 e control drugs were (+/-)-fenfluramine; (+)-fenfluramine; (-)-fenfluramine; its metabolites (+/-)-no

111 d obesity treatment before the withdrawal of fenfluramine for an association with heart valve regurgi

112 ts [56%]) were randomized to the 0.7-mg/kg/d fenfluramine group (n = 87), 0.2-mg/kg/d fenfluramine gr

113 g/d fenfluramine group (n = 87), 0.2-mg/kg/d fenfluramine group (n = 89), or placebo group (n = 87).

114 l [CI], 1.32-3.59), 13.7% in the phentermine/fenfluramine group (RR, 3.34; 95% CI, 2.09-5.35), and 4.

115 icacy end point: patients in the 0.7-mg/kg/d fenfluramine group achieved a -19.9 percentage points (9

116 More patients in the 0.7-mg/kg/d fenfluramine group achieved a 50% or greater response (2

117 ase in frequency of 45.7% in the 0.7-mg/kg/d fenfluramine group and 58.2% in the 0.2-mg/kg/d fenflura

118 fluramine group and 58.2% in the 0.2-mg/kg/d fenfluramine group compared with an increase of 3.7% in

119 howed that the rate of binge eating in the d-fenfluramine group fell three times more rapidly than th

120 month follow-up the binge frequency of the d-fenfluramine group had increased to pretreatment levels

121 nt scale to more patients in the 0.7-mg/kg/d fenfluramine group than patients in the placebo group (2

122 as 26.5 percentage points in the 0.7-mg/kg/d fenfluramine group, 14.2 percentage points in the 0.2-mg

123 p, 14.2 percentage points in the 0.2-mg/kg/d fenfluramine group, and 7.6 percentage points in the pla

124 hs (range, 1.4-63 months) in the phentermine/fenfluramine group, while the untreated group had no ano

125 t 10% of patients and more frequently in the fenfluramine groups) were decreased appetite, diarrhoea,

126 Fenfluramine has been reported to have antiseizure activ

127 Brain sites activated by D-fenfluramine have been mapped via the expression of the

128 le-dose, oral administration of 60 mg of d,l-fenfluramine hydrochloride (Pondimin).

129 free after a single-blind placebo and after fenfluramine hydrochloride administration on a second da

130 his study examines the prolactin response to fenfluramine hydrochloride challenge in young boys who s

131 administered the serotonin-releasing drug dl-fenfluramine in a placebo-controlled protocol to nine wo

132 sufficient to suppress the Fos response to D-fenfluramine in any region of the brain examined, includ

133 udy was to assess the efficacy and safety of fenfluramine in patients with Dravet syndrome.

134 s the efficacy of the appetite suppressant d-fenfluramine in the treatment of binge eating disorder.

135 e hypophagia and c-fos induction elicited by fenfluramine in wild-type mice, but not in the 5-HT1B kn

136 Appetite suppressants-most commonly fenfluramines-increase the risk of developing PPH (odds

137 ect of two different ambient temperatures on fenfluramine-induced 5-HT neurotoxicity.

138 s of fenfluramine were assessed by measuring fenfluramine-induced anorexia and fenfluramine discrimin

139 mulation of 5-HT1B receptors is required for fenfluramine-induced anorexia and suggest a role for the

140 It is likely that D-fenfluramine-induced Fos expression at various sites in

141 Both drugs inhibited D-fenfluramine-induced Fos expression in the cingulate cor

142 gional specificity of mechanisms mediating D-fenfluramine-induced Fos expression.

143 Neither drug reduced D-fenfluramine-induced Fos responses in several other brai

144 CSF) 5-hydroxyindoleacetic acid (5-HIAA) and fenfluramine-induced plasma prolactin levels are markedl

145 ta seemingly confirm that low CSF 5-HIAA and fenfluramine-induced plasma prolactin reflects chronic,

146 mine (also known as "ecstasy") and blunted d-fenfluramine-induced prolactin release, substantiating t

147 w that not only low CSF 5-HIAA and a blunted fenfluramine-induced prolactin response, but also blunte

148 Fenfluramine-induced serotonin neurotoxicity was assesse

149 Fenfluramine-induced serotonin/prolactin in the T-treate

150 tor, significantly and similarly reduced the fenfluramine-induced serotonin/prolactin response in the

151 tudy investigated whether 5-HT released by D-fenfluramine induces Fos expression in the brain by acti

152 dies in our laboratory have indicated that D-fenfluramine induces Fos in the hypothalamus and cortex

153 The present study determined whether D-fenfluramine induces the expression of Fos in the brain

154 tanserin, a 5-HT2A/2C antagonist, prior to d-fenfluramine injection.

155 ellum) were not significantly altered by the fenfluramine intervention.

156 t inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediate

157 D-Fenfluramine is a serotonin (5-hydroxytryptamine, 5-HT)

158 that use of dexfenfluramine and phentermine/fenfluramine is associated with an increase in the preva

159 Use of fenfluramines is associated with an increased risk of PP

160 ethylation reduced the neurotoxic potency of fenfluramine, it also reduced its pharmacologic activity

161 re (+/-)-fenfluramine; (+)-fenfluramine; (-)-fenfluramine; its metabolites (+/-)-norfenfluramine, (+)

162 rm MDMA use could lead to the development of fenfluramine-like VHD.

163 lts indicate that Fos response elicited by D-fenfluramine may be mediated by other receptors, in addi

164 Prolactin response to d-fenfluramine may be more sensitive than lumbar CSF 5-HIA

165 monstrates that repeated exposure to MDMA or fenfluramine may interfere with the ability of serotonin

166 setmelanotide, diethylpropion, sibutramine, fenfluramine, mazindol, phentermine, or orlistat A third

167 partially suppressed the stimulus effects of fenfluramine, mCPP, and MK 212 and almost fully attenuat

168 Plasma levels of fenfluramine, norfenfluramine, homovanillic acid (HVA),

169 lease in the brain mediates the effects of D-fenfluramine on Fos expression.

170 Although the effect of fenfluramine on locomotion was indistinguishable between

171 on or aortic regurgitation after exposure to fenfluramines on serial echocardiography between Decembe

172 orts of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for

173 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four month

174 The use of fenfluramine or dexfenfluramine, particularly for four m

175 We hypothesized that fenfluramine or its metabolite norfenfluramine and other

176 g/d or 0.2-mg/kg/d (maximum 26 mg/d) dose of fenfluramine or placebo.

177 did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (laco

178 ses; P<.001 vs controls); and 15 phentermine/fenfluramine patients (4.5% all decreases; P =.03 vs con

179 range, 13-26 months) and for 340 phentermine/fenfluramine patients was 18.7 months (range, 13-26 mont

180 studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline)

181 ought to determine the effect of phentermine-fenfluramine (phen-fen) on the prevalence of valvular he

182 Coadministration of phentermine and fenfluramine (phen/fen) effectively treats obesity and p

183 ize the link between the clinical failure of fenfluramine-phentermine (fen-phen) and the subsequent r

184 ies, we examined 1163 patients who had taken fenfluramine-phentermine and 672 control patients who ha

185 elation between the length of treatment with fenfluramine-phentermine and the prevalence of valvular

186 nts (4.3% [95% CI, 0.6% to 14.8%]) receiving fenfluramine-phentermine developed valvular heart diseas

187 valvular abnormalities in patients who took fenfluramine-phentermine primarily involve those who had

188 These cases arouse concern that fenfluramine-phentermine therapy may be associated with

189 Candidates for fenfluramine-phentermine therapy should be informed abou

190 be an association between these features and fenfluramine-phentermine therapy.

191 ed 12.3+/-7.1 months after the initiation of fenfluramine-phentermine therapy.

192 vular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac d

193 til the mid-1990s, when the off-label use of fenfluramine plus phentermine (fen-phen) and the approva

194 s taking the now-banned appetite suppressant fenfluramine (Pondimin, Redux).

195 In Dravet syndrome, fenfluramine provided significantly greater reduction in

196 nversely, pretreatment with the 5-HT agonist fenfluramine reduced postictal inhibition of the HCVR an

197 d-Fenfluramine reduced the frequency of binge eating by ob

198 istration of the serotonin-releasing drug dl-fenfluramine, relative to placebo.

199 55 had taken dexfenfluramine and phentermine/fenfluramine, respectively, continuously for 30 days or

200 xfenfluramine, has been withdrawn because of fenfluramine's and its isomer's association with valvula

201 These results indicate that fenfluramine's behavioral and neurotoxic effects, unlike

202 N-methylation could also be used to separate fenfluramine's neurotoxic and pharmacologic effects.

203 Fenfluramine significantly increased serotonin/prolactin

204 For patients with bulimia nervosa, the fenfluramine-stimulated increase in serum prolactin conc

205 ical depletion of serotonin and reduced with fenfluramine, suggesting that seizure-induced respirator

206 n studies have demonstrated toxic effects of fenfluramines that clinicians should be aware of when co

207 Doses of fenfluramines that produce signs of brain serotonin neur

208 prevented by pretreatment with fluoxetine or fenfluramine, the ability of DBS to suppress VCMs remain

209 with fenfluramines and the evidence linking fenfluramines to primary pulmonary hypertension (PPH).

210 ent study, we tested the ability of MDMA and fenfluramine treatment to alter the ability of the circa

211 3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs wit

212 The appetite-suppressant drug fenfluramine, usually given in combination with phenterm

213 Brain sites activated by D-fenfluramine via the release of 5-HT have been mapped vi

214 ency in patients who received 0.7 mg/kg/d of fenfluramine vs placebo.

215 Drug-lever responding after fenfluramine was dose-dependent.

216 ure subtype that appeared most responsive to fenfluramine was generalized tonic-clonic seizure (120 o

217 R) in the discriminative stimulus effects of fenfluramine was investigated.

218 tors is required for the anorectic effect of fenfluramine, we assessed food intake in wild-type and 5

219 contribute to the 5-HT1B-mediated effects of fenfluramine, we studied by immunohistochemistry the ind

220 Pharmacologic effects of fenfluramine were assessed by measuring fenfluramine-ind

221 50 patients with previous exposure to fenfluramines who had at least mild mitral regurgitation

222 the evidence associating dexfenfluramine and fenfluramine with valvulopathy.