[Benzodiazepine antagonism by RO 15-1788: psychometric, hormonal and biophysical parameters]

Ro 15-1788, a selective benzodiazepine (BZD) antagonist, is known to precipitate withdrawal reactions in BZD-pretreated animals. We examined whether a high dose of Ro 15-1788 can precipitate withdrawal reactions relating to behavior and changes in the stress-hormone plasma levels after acute BZD treatment in man. On two consecutive days, 15 min and 24 h respectively after a single treatment with either lormetazepam (0.06 mg/kg: LMZ group), flunitrazepam (0.03 mg/kg: FNZ group) or placebo (PLA group), 18 healthy volunteers received two injections of Ro 15-1788 (0.01 mg/kg). Behavioral responses (mood changes, anxiety), cortisol and prolactin plasma levels, and physiological parameters were examined. In all groups there were only slight changes in the circulation parameters. Minor anxiety reactions were seen after Ro 15-1788, which occurred the 1st day in the PLA group and the 2nd day in the BZD groups. Depression was noted especially in the FNZ group after both injections of Ro 15-1788. The physiological morning decrease in cortisol plasma level was influenced on the 1st day in the LMZ group (2 volunteers showed high plasma levels) and the 2nd day in the FNZ group: a slight increase of cortisol plasma level was measured after the 2nd injection of Ro 15-1788. Prolactin plasma levels arose immediately after LMZ injection and continued to increase after Ro 15-1788 injection. No increase in prolactin plasma levels was found in the other groups or in the LMZ group after the 2nd challenge by Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)