The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus-pituitary-adrenocortical system inelderly subjects

There is preclinical evidence that CRH is released in response to a glutama tergic stimulation. However, it is not clear, whether glutamate plays a rol e in the physiological stress response. We tested whether the antiglutamate rgic drug riluzole dampens the response of the hypothalamus-pituitary-adren ocortical (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 Blood was withdrawn every 15 min for estimati on of cortisol and ACTH from 14.00 to 20.00 h. Between 16.00 and 16.45 h, t he subjects were subjected to a cognitive challenge paradigm. Further, betw een 19.02 and 19.15 an individually adapted physical stress test was perfor med. After riluzole treatment, baseline ACTH and cortisol concentrations we re unchanged when compared to placebo treatment. Also, after the mental str essor, there was no difference between both treatment conditions. In contra st, the cortisol (riluzole vs. placebo: 148 +/- 60 vs. 183 +/- 98 nmol/l) a nd ACTH response (20.2 +/- 11.9 vs. 40.7 +/- 61.9 pmol/l) to the physical s tressor tended to be lower after riluzole pretreatment. In conclusion, the antiglutamatergic drug riluzole did not have any effects upon HPA system ac tivity under baseline and cognitive-stress-induced conditions in elderly su bjects. However, a trend for dampening the endocrine response to physical s tress emerged. Copyright (C) 2001 S. Karger AG. Basel.