CNS-related performance and haemodynamics of metoprolol-Oros and propranolol after single and 3 days dosing in healthy volunteers.
1. The effects of metoprolol-Oros 14/190 once daily, propranolol 80 mg twice daily and temazepam 10 mg once daily on central nervous system (CNS) related performance and haemodynamic variables were evaluated in a double-blind, randomized, placebo controlled, crossover study in 12 healthy volunteers. Drugs were administered for 3 consecutive days except for temazepam, which was administered on days 1 and 3 only. Treatment effects were evaluated at 0, 2, 5 and 8 h on days 1 and 3. 2. Neither beta-adrenoceptor blocker had significant effects in a battery of tests after single or 3 days dosing. Temazepam caused a decrease in saccadic peak velocity of 37.4 degrees s-1 (95% CI: 6.0, 68.9) at 2 h and an increase of auditory reaction times of 11.5 ms (0.2, 22.8) at 8 h on day 1. No significant effects of temazepam were detected on day 3. 3. Both beta-adrenoceptor blockers reduced exercise heart rate. Peak effects were measured at 2 h 40 min after propranolol but not metoprolol-Oros (difference, day 1:20 (11, 29) beats min-1, day 3:13 (8, 19) beats min-1). Both beta-adrenoceptor blockers significantly reduced baseline exercise heart rate on day 3. Compared with day 1, metoprolol-Oros caused larger reductions of exercise heart rate at all times on day 3. 4. Metoprolol-Oros and propranolol caused similar reductions of systolic- and diastolic blood pressure on days 1 and 3. Temazepam caused a small reduction in diastolic blood pressure at 5 h 40 min on day 1 but was otherwise devoid of haemodynamic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
van Steveninck
A L
AL
Centre for Human Drug Research, University Hospital, Leiden, The Netherlands.
Pieters
M S
MS
Schoemaker
H C
HC
Breimer
D D
DD
Cohen
A F
AF
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D013693:Temazepam / Q000008:administration & dosage / Q000494:pharmacology
D003692:Delayed-Action Preparations; D011433:Propranolol; D013693:Temazepam; D008790:Metoprolol