Hemodynamic effects of reboxetine
in healthy male volunteers.
Denolle T, Pellizzoni C, Jannuzzo MG, Poggesi I
Biotrial Research Centre, Rennes, France.
Clin Pharmacol Ther 1999 Sep; 66(3):282-7
ABSTRACT
BACKGROUND: Reboxetine [(R,S)-2[(R,S)-alpha-(2-ethoxyphenoxy)benzyl]morpholine methanesulfonate] is a racemic compound that consists of equal proportions of R,R- and S,S-enantiomers. This study investigated the hemodynamic effects of reboxetine and the R,R-enantiomer compared with placebo in volunteers. The pharmacokinetics of reboxetine and its enantiomers were also investigated in the study.
METHODS: Nine healthy, male volunteers received single doses of 4 mg reboxetine, 2 mg R,R-enantiomer, and placebo at weekly intervals. Reboxetine and the R,R-enantiomer were well tolerated in all volunteers.
RESULTS: The heart rates of patients in the supine and standing positions were increased after reboxetine administration compared with the R,R-enantiomer (P < .05, except supine heart rate at 6 hours) and placebo (P < .05). Supine systolic and diastolic blood pressure was also increased by 3 4 and 1 4 mm Hg, respectively, after reboxetine compared with R,R-enantiomer (-2 4 and -4 3 mm Hg) and placebo (-4 4 and -4 4 mm Hg) administration. The systolic and diastolic blood pressure measurements for subjects while standing did not differ significantly among treatments. There was no significant difference between the maximum plasma concentration, mean time to maximum plasma concentration, plasma half-life, or area under the plasma concentration-time curve (AUC) of the R,R-enantiomer after reboxetine or R,R-enantiomer administration. The ratio of the mean AUC values for the R,R- and S,S-enantiomers was 2.1.
CONCLUSION: These findings suggest that the S,S-enantiomer is responsible for the hemodynamic effects of reboxetine in humans. Increases in supine blood pressure after reboxetine administration may be interpreted as regression to the mean value and not caused by any treatment effect.
Reboxetine research
/ abstracts
1. Reboxetine
role in antidepressant therapy
2. Reboxetine
efficacy and tolerability
3. Reboxetine
clinical
pharmacologic profile
4. Inhibiting
the reuptake of noradrenaline and serotonin
5. Reboxetine
and depression in the elderly
6. Reboxetine
with severe major depressive disorder
7. Reboxetine
clinical
efficacy in major depression
8. Reboxetine
tolerability
and safety for major depression
9. Reboxetine
comparison with fluoxetine
10 Reboxetine
versus fluoxetine, impact on social functioning
11. Reboxetine versus
fluoxetine, differential effects
12. Reboxetine
prevents relapse in major depression
13 Reboxetine
efficacy compared with imipramine
14. Noradrenaline
reuptake inhibition
15. Antidepressants
noradrenergic
versus serotonergic
16. Reboxetine
in the treatment of bulimia
17.
Reboxetine
hemodynamic effects in healthy males
18. Reboxetine
effects of antidepressant therapy
19. Reboxetine
place in antidepressant
therapy
20. Reboxetine
stimulant effects in patients with narcolepsy
21. Reboxetine
selective noradrenaline reuptake inhibitor (NARI)
