ライフサイエンスコーパス: fenfluramine

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

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

3 significantly blunted prolactin response to fenfluramine.

4 order by measuring the prolactin response to fenfluramine.

5 the anorexia produced by an alternate agent, fenfluramine.

6 tinuation of dexfenfluramine and phentermine/fenfluramine.

7 ite-suppressant drugs, including phentermine-fenfluramine.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

22 D-Fenfluramine, a putative serotonin releaser and reuptake

23 Fenfluramine, a serotonin releaser and uptake inhibitor,

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

25 uring serotonin axonal markers 2 weeks after fenfluramine administration.

26 This difference was more pronounced after fenfluramine administration.

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

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

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

30 , 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of bra

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

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

33 Fenfluramine and dexfenfluramine have been demonstrated

34 Fenfluramine and dexfenfluramine were voluntarily withdr

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

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

37 announcement of the voluntary withdrawal of fenfluramine and dexfenfluramine.

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

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

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

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

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

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

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

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

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

47 Fenfluramine and phentermine have been individually appr

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

67 On serial echocardiography, fenfluramine-associated valvular regurgitation improved

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

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

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

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

72 Fenfluramine causes the release of serotonin proportiona

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

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

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

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

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

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

79 ly correlated with the prolactin response to fenfluramine challenge.

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

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

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

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

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

85 Appetite suppressants fenfluramine, dexfenfluramine, and phentermine have been

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

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

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

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

90 measuring fenfluramine-induced anorexia and fenfluramine discrimination.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

126 Fenfluramine-induced serotonin neurotoxicity was assesse

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

147 Although the effect of fenfluramine on locomotion was indistinguishable between

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

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

150 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four month

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

152 We hypothesized that fenfluramine or its metabolite norfenfluramine and other

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

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

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

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

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

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

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

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

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

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

163 Candidates for fenfluramine-phentermine therapy should be informed abou

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

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

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

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

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

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

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

171 55 had taken dexfenfluramine and phentermine/fenfluramine, respectively, continuously for 30 days or

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

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

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

175 Fenfluramine significantly increased serotonin/prolactin

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

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

178 Doses of fenfluramines that produce signs of brain serotonin neur

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

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

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

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

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

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

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

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

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

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

189 50 patients with previous exposure to fenfluramines who had at least mild mitral regurgitation

190 the evidence associating dexfenfluramine and fenfluramine with valvulopathy.