Neurobiology of an anorectic drug: Fenfluramine

Rowland, Neil E.; Carlton, Janis

doi:10.1016/0301-0082(86)90011-0

Cited by 312 publications

(114 citation statements)

References 185 publications

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“…Fenfluramine and serotonin-Although the effects of fenfluramine are quite similar to those previously reported for iontophoresed serotonin (Hurley and Pollak 2001), fenfluramine also releases norepinephrine at a lower affinity than serotonin (Rowland and Carlton 1986;Rothman et al 2003). In order to determine whether the effects of fenfluramine are mediated by serotonin, we directly compared the effects of fenfluramine and serotonin in 20 neurons.…”

Section: Are the Effects Of Fenfluramine Mediated By Serotonin Release?supporting

confidence: 55%

“…Fenfluramine is an amphetamine derivative with selectivity for the serotonergic system that in the short term increases serotonin levels in the brain but over the course of days or weeks may deplete serotonin (Rowland and Carlton 1986;Schwartz et al 1989;Baumann et al 2000;Tao et al 2002;Rothman et al 2003;Itzhak and Ali 2006). This study focuses on the effects of iontophoretically applied fenfluramine on the auditory responses of single IC neurons in a time frame of minutes.…”

Section: Introductionmentioning

confidence: 99%

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The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Hall

Hurley

2007

Hearing Research

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Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects.

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Section: Are the Effects Of Fenfluramine Mediated By Serotonin Release?supporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Hall

Hurley

2007

Hearing Research

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“…Fenfluramine stimulates prolactin release through in direct activation of postsynaptic receptors by the presynaptic release of endogenous 5-HT, as well as through inhibition of 5-HT reuptake (Garattini et al 1979;Rowland and Carlton 1986;Quattrone et al 1982).…”

Section: Discussionmentioning

confidence: 99%

Low Versus High Prolactin Responders to Fenfluramine Challenge: Marker of Behavioral Differences in Adult Male Cynomolgus Macaques

Botchin

Kaplan

Manuck

et al. 1993

Neuropsychopharmacol

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Prolactin response to acute administration of fenfluramine hydrochloride is considered an indirect assessment of "net" central serotonergic activity. This study compared behavioral characteristics of adult, male cynomolgus macaques (Macaca fascicularis) having "low" or "high" prolactin responses to fenfluramine challenge. The subjects were 75 animals housed in five-member social groups for 28 months. In month 23, prolactin responses to fenfiuramine challenge were evaluated. Obseroations of specific behaviors (aggressive, submissive, affiliative, and nonsocial) were made three times per week on animals in eIlch social group. The dominance status of each animal within a social group was assessed at weekly illtervals.Low prolactin respOllders had a significantly higher index KEY WORDS: Aggression; Serotonin; Fenfluramine; Prolactin; Cynomolgus macaques; Social behaviorStudies in human beings demonstrate a relationship between low serotonergic activity and the propensity for impulsive aggression among violent criminal offend-

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“…Nonetheless, no depletions of monoamines were noted; whether this was related to drug-induced hypothermia, a protective effect with most substituted amphetamines, is not yet known and will require treating animals at different ambient temperatures to resolve. It should be noted, however, that increases in body temperature are not always required for depletions of monoamines as fenfluramine induces hypothermia and depletes serotonin without an increase in GFAP (Miller and O'Callaghan, 1995;O'Callaghan and Miller, 1994;Rowland et al, 1993;Rowland and Carlton, 1986;Skelton et al, 2004;Stewart and Slikker, 1999). The lack of depletions in monoamines and the hypothermia suggest that 5-MEO-DIPT does not induce neurotoxicity to monoaminergic neurons; however, effects on other neurotransmitters are unknown.…”

Section: Effects Of 5-meo-diptmentioning

confidence: 99%

Alterations in Body Temperature, Corticosterone, and Behavior Following the Administration of 5-Methoxy-Diisopropyltryptamine (‘Foxy’) to Adult Rats: a New Drug of Abuse

Williams

Herring

Schaefer

et al. 2006

Neuropsychopharmacol

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Many drugs are used or abused in social contexts without understanding the ramifications of their use. In this study, we examined the effects of a newly popular drug, 5-methoxy-diisopropyltryptamine (5-MEO-DIPT; 'foxy' or 'foxy-methoxy'). Two experiments were performed. In the first, 5-MEO-DIPT (0, 10, or 20 mg/kg) was administered to rats four times on a single day and animals were examined 3 days later. The animals that received 5-MEO-DIPT demonstrated hypothermia during the period of drug administration and delayed mild hyperthermic rebound for at least 48 h. Corticosterone levels in plasma were elevated in a dose-dependent manner compared to saline-treated animals with minor changes in 5-HT turnover and no changes in monoamine levels. In experiment 2, rats were examined in behavioral tasks following either 0 or 20 mg/kg of 5-MEO-DIPT. The animals treated with 5-MEO-DIPT showed hypoactivity and an attenuated response to ( + )-methamphetamine-induced stimulation (1 mg/kg). In a test of path integration (Cincinnati water maze), 5-MEO-DIPT-treated animals displayed deficits in performance compared to the saline-treated animals. No differences were noted in the ability of the animals to perform in the Morris water maze or on tests of novel object or place recognition. The data demonstrate that 5-MEO-DIPT alters the ability of an animal to perform certain cognitive tasks, while leaving others intact and disrupts the endocrine system. 5-MEO-DIPT may have the potential to induce untoward effects in humans.

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Neurobiology of an anorectic drug: Fenfluramine

Cited by 312 publications

References 185 publications

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Low Versus High Prolactin Responders to Fenfluramine Challenge: Marker of Behavioral Differences in Adult Male Cynomolgus Macaques

Alterations in Body Temperature, Corticosterone, and Behavior Following the Administration of 5-Methoxy-Diisopropyltryptamine (‘Foxy’) to Adult Rats: a New Drug of Abuse

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