The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus-pituitary-adrenocortical system in elderly subjects.
There is preclinical evidence that CRH is released in response to a glutamatergic stimulation. However, it is not clear, whether glutamate plays a role in the physiological stress response. We tested whether the antiglutamatergic drug riluzole dampens the response of the hypothalamus-pituitary-adrenocortical (HPA) system to both a mental and a physical stressor. Nine male elderly healthy subjects received placebo and 150 mg riluzole for 2 days in a randomized balanced order. Blood was withdrawn every 15 min for estimation of cortisol and ACTH from 14.00 to 20.00 h. Between 16.00 and 16.45 h, the subjects were subjected to a cognitive challenge paradigm. Further, between 19.02 and 19.15 an individually adapted physical stress test was performed. After riluzole treatment, baseline ACTH and cortisol concentrations were unchanged when compared to placebo treatment. Also, after the mental stressor, there was no difference between both treatment conditions. In contrast, the cortisol (riluzole vs. placebo: 148 +/- 60 vs. 183 +/- 98 nmol/l) and ACTH response (20.2 +/- 11.9 vs. 40.7 +/- 61.9 pmol/l) to the physical stressor tended to be lower after riluzole pretreatment. In conclusion, the antiglutamatergic drug riluzole did not have any effects upon HPA system activity under baseline and cognitive-stress-induced conditions in elderly subjects. However, a trend for dampening the endocrine response to physical stress emerged.
Kniest
A
A
Central Institute of Mental Health, Mannheim, Germany.
Wiesenberg
C
C
Weber
B
B
Colla
M
M
Heuser
I
I
Deuschle
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D003071:Cognition; D018592:Cross-Over Studies; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D019782:Riluzole / Q000494:pharmacology*; D016037:Single-Blind Method; D013312:Stress, Physiological / Q000503:physiopathology; D013315:Stress, Psychological / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D019782:Riluzole; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone