Peripheral hormonal responses to D-fenfluramine as a probe of central serotonergic function in humans.
We tested the hypothesis that D-fenfluramine (DFEN)-elicited cortisol (CORT) release in humans may be mediated by a direct effect on the adrenal gland by pretreating subjects with dexamethasone (DEX), to prevent release of ACTH from the pituitary, followed by a DFEN challenge test. Eight healthy subjects (four males; four female) (mean age = 38.1 +/- 8.4 years (SD)] were studied > 1 week apart (same phase of menstrual cycle) and testing order was randomised. On the with-DEX day (DEX+), subjects took 2 mg DEX orally at 10 p.m.; 30 mg DFEN was then given orally at 9 a.m. and samples were taken at 0-5 h for PRL and CORT. Peak hormone responses (delta values) were calculated by subtracting baseline values from the maximum levels post-DFEN administration. Peak and baseline hormonal values were compared between the two test conditions; DFEN-induced CORT and PRL responses were compared across all time points, with and without DEX. There was no significant difference in delta PRL between the two test conditions (DEX- and DEX+), but delta CORT values were significantly reduced after DEX: mean delta CORT DEX- = 68.4 +/- 26.3 nmol/l; DEX+ = 0.0 nmol/l (all blunted) (df 7,1; P = 0.03). The completely blunted peripheral cortisol response indicates that DFEN cortisol responses are of central origin only.
Abel
K M
KM
Department of Psychological Medicine, King's College School of Medicine and Dentistry and the Institute of Psychiatry, London, UK. sphakma@iop.bpmf.ac.uk
Cleare
A J
AJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*
D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone