Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine

McCann, Una D.; Eligulashvili, Victoria; Ricaurte, George A.

doi:10.1016/s0278-5846(98)00063-3

Cited by 13 publications

(3 citation statements)

References 21 publications

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“…At the time of approval, it was generally accepted that dexfenfluramine did not increase the risk of neuropsychiatric adverse effects [18,19]; however, a review of some individual case reports indicate adverse events including mood swings, depression and anxiety [20]. Studies conducted with sibutramine indicate that it has a low risk profile for neuropsychiatric adverse effects.…”

Section: The Monoamine System: Indirect Agonists and Subtype Selectivmentioning

confidence: 99%

Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs

Nathan

O’Neill

Napolitano

et al. 2011

CNS Neuroscience & Therapeutics

104

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Section: The Monoamine System: Indirect Agonists and Subtype Selectivmentioning

confidence: 99%

Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs

Nathan

O’Neill

Napolitano

et al. 2011

CNS Neuroscience & Therapeutics

104

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“…With the exception of a retrospect clinical study (31 cases with a Fen or dexFen intake history) (cf. McCann et al, 1998), the literature does not contain any reliable data on the postulated CNS neurotoxicity potential of Fen in the human under clinically used dosing regimens.…”

Section: Fenfluramine "Neurotoxicity"mentioning

confidence: 99%

Serotonin neurotoxins — past and present

Baumgarten

Lachenmayer

2004

neurotox res

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Autoxidation pathways and redox reactions of dihydroxytryptamines (5,6- and 5,7-DHT) and of 6-hydroxydopamine (6-OH-DA) are illustrated, and their potential role in aminergic neurotoxicity is discussed. It is proposed that certain aspects of the cytotoxicity of 6-OH-DA and of the DHTs, namely redox cycling of their quinone- and quinoneimine-intermediates as a source of free radicals, may also apply to quinoidal reactive intermediates and to glutathionyl- or cysteinyl conjugates ("thioether adducts") of o-dihydroxylated (catechol-like) metabolites of certain substituted amphetamines (of methylenedioxymethamphetamine (MDMA) and of methylenedioxyamphetamine (MDA)). Despite similarities in their primary interaction with the plasmalemmal (serotonergic transporter/dopamine transporter, SERT/DAT) and vesicular monoamine transporters (VMAT2), MDMA and fenfluramine (N-ethyl-meta-trifluoromethamphetamine, Fen) differ substantially in many aspects of their metabolism, pharmacokinetics, pharmacology, and neurotoxicology profile; the consequences of these differences for neuronal response patterns and long-term survival prospects are not yet fully understood. However, sustained hyperthermia appears to be a critical factor in these differences. Methodological requirements for adequate detection and description of pre- and postsynaptic forms of drug-induced neurotoxicity are exemplified using recently published accounts. The inclusion of microglial markers into research strategies has widened contemporary pathogenetic concepts on methamphetamine (MA)-induced neurotoxicity as an example of inflammatory neurodegeneration, thus complementing the traditional ROS and RNS-dependent stress models. Amphetamine-type neurotoxicity studies may assist in elaborating of preventive strategies for human neurodegenerative disorders.

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“…Conceptually, serotonergic neurodegeneration induced by methylenedioxy‐substituted amphetamines may be problematic, considering that psychiatric disorders such as depression and panic disorder, and also behavioural disturbances such as aggression and impulsivity, are associated with low 5‐HT (see Apter et al ., 1990). In this regard there have been a number of reported cases where users of drugs which elicit serotonergic neurotoxicity, such as MDMA and fenfluramine, have presented with a variety of psychiatric symptoms including depression and panic attacks (McCann & Ricaurte, 1991; Series et al ., 1994; McCann et al ., 1998b).…”

Section: Introductionmentioning

confidence: 99%

Methylenendioxyamphetamine produces serotonin nerve terminal loss and diminished behavioural and neurochemical responses to the antidepressant fluoxetine

Harkin

Shanahan

Kelly

et al. 2003

Eur J of Neuroscience

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The effect of prior exposure to methylenedioxyamphetamine (MDA) on behavioural and neurochemical responses to fluoxetine were assessed in a rat model of antidepressant action. MDA (7.5 mg/kg, i.p.) was administered to rats twice daily for 4 consecutive days, and 4 weeks later the behavioural effect of fluoxetine (5 or 20 mg/kg; i.p. x 3) was examined in the modified rat forced-swimming test. In addition, the ability of fluoxetine to reduce serotonin (5-HT) metabolism was measured as an index of its efficacy in inhibiting 5-HT reuptake in vivo. In vehicle-treated rats, fluoxetine (5 and 20 mg/kg) produced a characteristic increase in swimming behaviour in the forced-swimming test. In contrast, fluoxetine-induced swimming was markedly attenuated in MDA-treated rats. MDA pretreatment resulted in 5-HT nerve terminal degeneration, indicated by reduced 5-HT and 5-HIAA concentrations in the frontal cortex, amygdala and hippocampus, and reduced [3H]paroxetine binding in the frontal cortex. In vehicle-treated rats, fluoxetine (5 and 20 mg/kg) decreased 5-HT metabolism (5-HIAA : 5-HT ratio) in the frontal cortex, amygdala and hippocampus. MDA pretreatment attenuated the ability of fluoxetine to reduce 5-HT metabolism in all brain regions examined. These findings are the first to demonstrate that prior exposure to the methylenedioxy-substituted amphetamine MDA results in diminished responsiveness to the antidepressant fluoxetine.

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Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine

Cited by 13 publications

References 21 publications

Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs

Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs

Serotonin neurotoxins — past and present

Methylenendioxyamphetamine produces serotonin nerve terminal loss and diminished behavioural and neurochemical responses to the antidepressant fluoxetine

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