Differential effects of flumazenil (an antagonist) and midazolam (an antagonist at the benzodiazepine receptor) were studied in 8 healthy males. Adrenocorticotropic hormone (ACTH) and cortisol responses to a corticotropin-releasing hormone (CRH) challenge were measured. ACTH response was significantly lower after flumazenil administration than after saline or midazolam. No significant treatment effect was found for the CRH-induced cortisol secretion. Our results agree with previous reports that point to an agonistic effect of flumazenil on pituitary-adrenocortical system activity and, moreover, may further support the anxiolytic activity of flumazenil in stimulated stress.
