Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15-1788.
Noradrenaline (NA) plasma levels were examined in 18 healthy volunteers on 2 consecutive days after a single treatment with either lormetazepam (0.06 mg/kg) (LMZ group), flunitrazepam (0.03 mg/kg) (FNZ group) or placebo (PLA group) in combination with the benzodiazepine (BZ) antagonist Ro 15-1788 (0.1 mg/kg). Behavioural responses (mood changes, anxiety) were also investigated in parallel. Both BZ decreased NA plasma levels to 50% of the basal values 10 min after the injection; administration of Ro 15-1788 15 min later reinstated NA plasma levels to basal values. A second administration of Ro 15-1788 (0.1 mg/kg) 24 h after BZ or PLA treatment increased NA plasma levels, estimated 10 min after the injection in both the LMZ- and the FNZ groups, but not in the PLA group. Behavioural responses measured under the same treatment also indicated minor anxiety responses followed by mood impairment. These data suggest that a stressful situation may be precipitated by the antagonist Ro 15-1788 24 h after a single BZ treatment, which resembles a withdrawal response, and increases NA plasma levels.
D000328:Adult; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000378:metabolism; D001569:Benzodiazepines; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004562:Electrocardiography; D004569:Electroencephalography; D005442:Flumazenil / Q000494:pharmacology*; D005445:Flunitrazepam / Q000494:pharmacology; D006801:Humans; D008140:Lorazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011897:Random Allocation
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D005442:Flumazenil; D005445:Flunitrazepam; C023842:lormetazepam; D008140:Lorazepam; D009638:Norepinephrine