ISSN:
1440-1681
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
1. Fenfluramine is an optically active 5-hydroxytryptamine (5-HT) releaser and re-uptake inhibitor. Increased brain 5-HT mediates appetite suppression, the d enantiomer being more active than l- or dl-fenfluramine. Fenfluramine also stimulates the hypothalamic-pituitary-adrenal (HPA) axis, leading to suggestions that this could act as a marker for its biological actions. However, the d enantiomer appears less active than a comparable dl racemate dose in animals, while effects of D-fenfluramine on the human HPA axis remain unproven. The aim of the present study was to clarify this.2. Seven healthy human volunteers (three male, four female; 18-58 years) received 30 mg oral D -fenfluramine or placebo, followed by 125 p-g/kg, i.v. naloxone or placebo, in randomized, double-blinded, placebo-controlled afternoon studies. We measured plasma adrenocorticotropic hormone (ACTH) and Cortisol levels in samples taken at intervals throughout the study period.3. In contrast to previous results with dl-fenfluramine, we found no dynamic responses to d -fenfluramine alone and no augmentation of responses to naloxone.4. Central pathways to HPA axis activation are apparently not stimulated by d -fenfluramine at this dose in humans, in contrast with dl-fenfluramine, where the l enantiomer may be more selective for proposed corticotropin-releasing hormone-mediated, post-synaptic 5-HT2 or noradrenergic mechanisms. As previously reported, d-fenfluramine significantly blunted the circadian fall in basal plasma Cortisol, providing in vivo evidence for serotonergic involvement in circadian regulation.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1440-1681.1998.tb02263.x
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