No abstract

and lInstitute of Psychosomatic Research, Herbsthalde 11, 7000 Stuttgart 1 FRG 1 The possible interaction (as indicated by rat experiments) between calcium channel blocking agents and benzodiazepines has been evaluated in nine healthy subjects. 2 Subsequently to an intravenous loading dose (0.07 mg kg-1) midazolam was infused for 6 h (0.035 mg kg-' h-1) and steady state plasma levels between 54 to 114 ,ug 1-1 were achieved. Two hours after the bolus of midazolam a solution of 20 mg nitrendipine or placebo was administered in a randomized, double-blind crossover fashion. 3 The marked sedative-hypnotic effects of midazolam as assessed by visual analogue scales (about four fold increase in the sedation index) and choice reaction time (100% prolongation) indicated some form of adaptation or tolerance towards the end of the infusion. However, the midazolam-induced impairments were not affected by nitrendipine. 4 EEG-data indicated stabile benzodiazepine-like effects during the complete infusion period of midazolam (e.g. decrease in alpha activity, increase in sigma, delta 2 and beta 1 activity). Again, these alterations were not modified by nitrendipine. 5 There was also no pharmacokinetic interaction between both agents, since elimination of midazolam (t½ -2.5 ± 0.8 h; CL -548 ± 143 ml min-') was in close agreement with control values (t½ = 2.4 ± 0.6 h; CL = 512 ± 102 ml min-'). Likewise, plasma levels of nitrendipine were comparable to literature data. 6 Thus, it could be concluded that nitrendipine does not affect the action of midazolam and therefore a direct involvement of calcium at the benzodiazepine receptor site is unlikely under our clinical conditions.