Neurohormonal responses to D-fenfluramine in healthy elderly subjects. A placebo-controlled study.
Considering age-related changes in serotonin (5HT) function, we examined normative data of prolactin (PRL) and cortisol (CORT) responses to D-fenfluramine (D-FEN) in healthy elderly subjects. Twenty-three healthy male and female volunteers aged 60-86 participated in a single-blind, placebo-controlled, fixed-order, crossover-design challenge test. Two baseline PRL and CORT values and the responses of these hormones to 30 mg of oral D-FEN and placebo over a 4 h period were measured on two separate sessions. PRL and CORT responses were significantly greater following D-FEN than after placebo. Peak PRL responses (maximum change from baseline following D-FEN) were relatively robust compared to peak CORT responses. Peak PRL concentration was positively correlated with plasma D-nor-FEN concentration. Gender and aging had no effect on hormonal responses in the elderly. Although the weight adjusted dose used in this study was higher than the therapeutic dose of D-FEN, PRL responses were modest and only two participants experienced side effects. D-FEN is a safe serotonergic probe and PRL responsivity to D-FEN is a reliable index of central 5HT function in the elderly. An age-related decline in serotonergic function must be considered in determining the dose requirement for maximal hormonal responses to D-FEN challenge tests in the elderly.
Ramasubbu
R
R
Department of Psychiatry, University of Ottawa, Royal Ottawa Hospital, Ont., Canada. rramasub@rohcg.on.ca
Flint
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A
Brown
G
G
Awad
G
G
Kennedy
S
S
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001519:Behavior / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D012727:Sex Characteristics
D005277:Fenfluramine; D006854:Hydrocortisone; D018377:Neurotransmitter Agents; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors