A comparison of the acute effects of dextroamphetamine and fenfluramine in depression

Ward, Nicholas G.; Ang, Jessy; Pavinich, Gary

doi:10.1016/0006-3223(85)90007-1

Cited by 13 publications

(3 citation statements)

References 38 publications

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“…Indeed, several small-scale studies support this notion. Rickels et al (1976) reported that ( ± )-fenfluramine reduced emotional symptoms in obese patients, while Ward et al (1985) suggested that acute administration of (+)-fenfluramine to depressed patients produced antidepressant-like effects. Similarly, a small double-blind placebo-controlled crossover clinical trial (18 patients) indicated that (+)-fenfluramine effectively treated seasonal affective disorder (O'Rourke et al, 1989).…”

Section: Potential Therapeutic Indicationsmentioning

confidence: 99%

Serotonin releasing agents

Rothman

Baumann

2002

Pharmacology Biochemistry and Behavior

126

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This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine (mCPP), a major metabolite of the antidepressant drug trazodone. Findings from in vitro and in vivo studies support the hypothesis that fenfluramines and mCPP release neuronal 5-HT via a non-exocytotic carrier-mediated exchange mechanism involving 5-HT transporters. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of developing valvular heart disease (VHD), whereas the latter activity is implicated in the anorectic effect of systemic fenfluramine. Anorectic agents that increase the risk of developing primary pulmonary hypertension (PPH) share the common property of being 5-HT transporter substrates. However, these drugs vary considerably in their propensity to increase the risk of PPH. In this regard, neither trazodone nor mCPP is associated with PPH. Similarly, although some 5-HT substrates can deplete brain 5-HT (fenfluramine), others do not (mCPP). In addition to the established indication of obesity, 5-HT releasers may be helpful in treating psychiatric problems such as drug and alcohol dependence, depression and premenstrual syndrome. Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders.

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Section: Potential Therapeutic Indicationsmentioning

confidence: 99%

Serotonin releasing agents

Rothman

Baumann

2002

Pharmacology Biochemistry and Behavior

126

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“…Besides other serotonergic compounds (Murphyet al, 1986) dl-FEN may therefore serve as a neuropharmacologic probe of the central serotonergic system (Rowland and Carlton, 1986). Fenfluramine is used clinically as an anorexigent agent and there are also some reports about its antidepressant efficacy ( Ward et al, 1985;O'Rourke et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Multiple Hormone Responses to Stimulation with dl-Fenfluramine in Patients with Major Depression before and after Antidepressive Treatment

Kasper

Vieira²,

Schmidt³

et al. 1990

Pharmacopsychiatry

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The authors investigated 31 drug-free inpatients with major depression using dl-fenfluramine (dl-FEN) as a serotonin probe (fenfluramine stimulation test, FFT). The FFT was performed in the same individuals (intraindividual comparison) with and without application of dl-FEN and before and after antidepressive treatment. Blood samples were analyzed for prolactin, cortisol, thyrotropin (TSH), growth hormone (HGH), dl-FEN and its major metabolite dl-norfenfluramine. There was no difference in the conditions before and after treatment as regards peak plasma levels of dl-FEN. Compared with saline, significant (P less than 0.01) increases were detected for dl-FEN-stimulated cortisol and prolactin values. A significantly (P less than 0.01) lower increase in dl-FEN-stimulated prolactin values was found after treatment compared with the situation before treatment, a finding which was dependent on the type of medication which the patients were receiving at the time when the test procedure took place. Baseline and dl-FEN-stimulated cortisol values were significantly (P less than 0.001) lower and TSH values were significantly (P less than 0.01) higher in the condition after compared with the one before treatment. Patients' mean peak delta prolactin responses to dl-FEN before treatment were significantly (P less than 0.05) correlated with those of patients after subchronic treatment with fluvoxamine. Hormonal responses were neither associated with the severity of the illness nor with a specific psychopathological profile.

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“…In contrast, although /-fen fluramine has no activity on the binding of D1 or D2 dopamine receptors it decreases striatal dopamine concentrations and increases the me tabolite homovanillic acid [Jori et al, 1973;Invernizzi et al, 1986]. In freely moving rats, in vivo dialysis experi ments have shown increased release of dopamine and its metabolites (homovanillic acid and DOPAC) from the striatum [Bettini et al, 1987], At low doses, /-fenflura mine is able to antagonize amphetamine-induced stereo typy and hyperactivity, but only at high doses is it able to block apomorphine-induced stereotypy [Bendotti et al, 1980], There is also evidence that /-fenfluramine is sed ative, as it reduced motor activity of mice and rats [Le Douarec et al, 1966], Clinical evidence suggests that fenfluramine de creases depression, agitation and aggression [Ward and Pavinich, 1985;Campbell et al, 1986;Ritvo et al, 1986] and, in autistic and obese patients, anxiety [Gaind, 1969;Rickels et al, 1976;De Villard et al, 1986], So far there have been no clinical reports for the effects of the /-isomer and thus the contribution of each isomer to the clinical actions of the racemate cannot be assessed. The following experiments were therefore conducted in order to determine whether the /-isomer of fenfluramine pos sessed antiaggressive and/or anxiolytic activity in animal tests.…”

Section: Introductionmentioning

confidence: 99%

<i>l</i>-Fenfluramine in Tests of Dominance and Anxiety in the Rat

File

Guardiola‐Lemaître²

1988

Neuropsychobiology

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l-Fenfluramine (1.25 and 2.5 mg/kg) significantly reduced the success of dominant rats competing with untreated middle rank rats for chocolate. In resident rats, l-fenfluramine (2.5 mg/kg) significantly increased the number of submissions, and the time spent submitting, to untreated rats intruding into their home-cage territory; it also significantly reduced the number of kicks directed at, and the time spent kicking, the intruder; and the incidence of, and time spent in, aggressively grooming the intruder. When the intruder rats were treated with l-fenfluramine the only significant change was a decrease in the number of wrestling bouts and the time spent wrestling. Since l-fenfluramine did not change other behaviours in this test (e.g. sniffing the opponent) the decrease in dominance behaviours was probably not secondary to nonspecific sedation. In the social interaction test of anxiety, l-fenfluramine (2.5 and 5 mg/kg) significantly reduced the time spent in active social interaction, and decreased motor activity. Analyses of covariance indicated that these were two independent effects. In the elevated plus-maze, l-fenfluramine (1.25–5 mg/kg) significantly decreased the percent number of entries made onto open arms, and (2.5 and 5 mg/kg) significantly decreased the percent of time spent on the open arms. The total number of arm entries was reduced by all doses (0.625–5 mg/kg). Analysis of covariance indicated that the decrease in percent of time spent on the open arms was secondary to the drop in overall activity. Thus there was no evidence of anxiolytic action in either of these tests, the changes indicating, if anything, anxiogenic effects. Clinically, the racemate has been reported to have antiaggressive and anxiolytic effects. The results of the present study suggest that the former, but not the latter, effect might lie in the action of the l-isomer.

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A comparison of the acute effects of dextroamphetamine and fenfluramine in depression

Cited by 13 publications

References 38 publications

Serotonin releasing agents

Serotonin releasing agents

Multiple Hormone Responses to Stimulation with dl-Fenfluramine in Patients with Major Depression before and after Antidepressive Treatment

<i>l</i>-Fenfluramine in Tests of Dominance and Anxiety in the Rat

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