Increased plasma prolactin levels induced in rats by d-fenfluramine: Relation to central serotonergic stimulation

Quattrone, Aldo; Renzo, Gianfranco Di; Schettini, Gennaro; Tedeschi, G; Scopacasa, Francesco

doi:10.1016/0014-2999(78)90073-0

Cited by 59 publications

(13 citation statements)

References 22 publications

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“…A double dose was unable to potentiate the PRL secretion suggesting that the dose employed in this study, commonly used in clinical practice, is already at the maximal action level. A similar serotoninergic stimulatory effect on rat PRL secretion has been previously reported [14,15,40,41].…”

Section: Discussionsupporting

confidence: 51%

Depending on the Stimulus, Central Serotoninergic Activation by Fenfluramine Blocks or Does not Alter Growth Hormone Secretion in Man

Casanueva¹,

Villanueva²,

Peñalva³

et al. 1984

Neuroendocrinology

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The role of serotonin (5-HT) in the hypothalamic regulation of human growth hormone (GH) was reassessed through the use of fenfluramine, which selectively releases 5-l·lT from presynaptic terminals. Oral administration of L-dopa plus propranolol induced a potent and sustained GH release in the subjects tested (26 ± 6 ng/ml). The administration of fenfluramine (20 mg i.v. as bolus plus 20 mg/30 min i.v.) completely suppressed the L-dopa-induced GH secretion (2 ± 0.5 ng/ml). On the other hand, when arginine (30 g/30 min i.v.) was used as a GH stimulant of medium intensity (12.7 ± 2.8 ng/ml), fenfluramine at the same dose was not able to alter the pattern of pituitary secretion (11.5 ± 4.2 ng/ml). Fenfluramine alone induced a slight nonsignificant decrease in GH values with a parallel and significant increase in prolactin (PRL) secretion in accordance with the proposed serotoninergic activity of the drug. Rat PRLsecretion by pituitaries incubated in vitro was inhibited by dopamine. Fenfluramine added to the system did not counteract the dopaminergic reduction of PRL release, making unlikely the possibility of an antagonism at the dopaminergic receptor as mechanism of action of fenfluramine on PRL secretion. In conclusion, depending on the stimulus under study, serotoninergic activation by fenfluramine either inhibits or does not alter GH secretion in man. No proof of a serotoninergic stimulatory component on GH regulation has been detected in this study. Fenfluramine is a valuable tool in neuroendocrinological studies, dealing with serotoninergic mechanisms.

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Section: Discussionsupporting

confidence: 51%

Depending on the Stimulus, Central Serotoninergic Activation by Fenfluramine Blocks or Does not Alter Growth Hormone Secretion in Man

Casanueva¹,

Villanueva²,

Peñalva³

et al. 1984

Neuroendocrinology

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“…The observation of a robust PRL response to FEN in these subjects indicates that the dose of FEN (60 mg p.o.) used was sufficient to stimulate a 5-HT-mediated neuroendocrine response as reported in previous an imal and clinical studies [1,28,29,34,36].…”

Section: Discussionmentioning

confidence: 71%

“…FEN is a centrally active 5-HT-releasing and 5-HT reuptake inhibiting agent [6. 12, 13], Its stimulatory effects on the central 5-HT system -vis-à-vis changes in cerebro spinal fluid 5-hydroxyindoleacetic acid and plasma prolac tin (PRL) -after acute administration have been demon strated in animal [28,29] and clinical studies [1,34,36], Un like 5-HTP or zimelidine, however, FEN has little demon strable effect on the release of central catecholamines [1,4,12], The results of this study suggest that central 5-HT may not play a significant stimulatory or inhibitory role in the release of pituitary TSH in euthyroid men. …”

mentioning

confidence: 99%

Central Serotoninergic Stimulation by Fenfluramine Challenge Does Not Affect Plasma Thyrotropin-Stimulating Hormone Levels in Man

et al. 1988

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Thyrotropin-stimulating hormone (TSH) and prolactin (PRL) responses to an acute oral challenge of fenfluramine (60 mg), a central serotoninergic (5-hydroxytryptamine) releasing/uptake inhibiting agent, were examined in 8 healthy males in order to assess the role of central serotoninergic stimulation in the release of TSH. Plasma PRL, but not TSH, was significantly elevated by fenfluramine. These data suggest that central serotoninergic activity does not play an important role in the physiologic release of plasma TSH in man. Further, thyrotropin-releasing hormone is unlikely to be the PRL-releasing factor involved in the fenfluramine-induced stimulation of PRL.

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“…It has been reported that 5-HT precursors, such as Ltryptophan and 5-hydroxytryptophan (5-HTP), significantly increased plasma PRL levels in rats (Lu & Meites, 1973;Marchlewska-Koj & Krulich, 1975) while substances which deplete brain 5-HT content, such as p-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine (5,7-DHT), have been found to decrease PRL secretion in the same animal species (Quattrone et al, 1978;Wuttke etal., 1977). Recently, it has also been shown that quipazine and (+)-fenfluramine, two 5-HT agonists (Fuxe et al, 1975b;Garattini et al, 1975;Samanin et al, 1976), significantly stimulated PRL release in rats by acting through a 5-HT mechanism in the brain (Quattrone et al, 1978(Quattrone et al, , 1979a. Thus the evidence supports the stimulatory role of central 5-HT neurones in the control of PRL release.…”

Section: Introductionmentioning

confidence: 99%

Prolactin secretion in man: a useful tool to evaluate the activity of drugs on central 5‐hydroxytryptaminergic neurones. Studies with fenfluramine.

Quattrone¹,

Tedeschi²,

Aguglia³

et al. 1983

Brit J Clinical Pharma

157

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1 Acute oral administration of various doses of fenfluramine, a 5-HT releaser, induced a doserelated increase of PRL secretion in nine healthy volunteers. 2 Fenfluramine reached the maximum effect on PRL secretion at 4 h after its administration. This effect was already significant at 2 h and lasted till 8 h. 3 Metergoline, a 5-HT receptor blocker, when administered alone, decreased serum PRL levels in six healthy subjects. The pretreatment with this drug significantly antagonized the PRL-releasing action of fenfluramine (60 mg) suggesting that the effect of fenfluramine on PRL release may be mediated through a 5-HT mechanism in the brain. 4 These findings suggest the possibility that serum PRL levels in humans may represent a useful tool to evaluate, in vivo, the activity of drugs possessing putative 5-hydroxytryptaminergic properties.

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Increased plasma prolactin levels induced in rats by d-fenfluramine: Relation to central serotonergic stimulation

Cited by 59 publications

References 22 publications

Depending on the Stimulus, Central Serotoninergic Activation by Fenfluramine Blocks or Does not Alter Growth Hormone Secretion in Man

Depending on the Stimulus, Central Serotoninergic Activation by Fenfluramine Blocks or Does not Alter Growth Hormone Secretion in Man

Central Serotoninergic Stimulation by Fenfluramine Challenge Does Not Affect Plasma Thyrotropin-Stimulating Hormone Levels in Man

Prolactin secretion in man: a useful tool to evaluate the activity of drugs on central 5‐hydroxytryptaminergic neurones. Studies with fenfluramine.

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