Comparisons of beta-adrenergic blocking properties of S- and R-timolol in humans.
In animals, the R-enantiomer of timolol causes a significant reduction in intraocular pressure but had only 1/80 the activity of the S-enantiomer at extraocular receptors. The beta 1- and beta 2-adrenoceptor blocking properties of orally administered R- and S-timolol were compared in a double-blind placebo controlled trial in two groups of healthy men. Each subject in group A (n = 6) received placebo, 1 and 3 mg S-timolol and 25 and 75 mg R-timolol in random order, group B (n = 5) received placebo, 0.5, and 1 mg S-timolol and 3 and 10 mg R-timolol. In both groups, R- and S-timolol comparably inhibited isoproterenol-induced increases in heart rate (P < .05), forearm blood flow (P < .05, except at 3 micrograms/minute of isoproterenol after the R-doses in group B), and finger tremor (P < .05) in comparison with placebo. The findings for the R-enantiomer in this study were unexpected based on the animal studies and previous studies that demonstrated marked differences in beta blocking effects of other beta-blockers in which the R-enantiomers were less inhibitory.
Rotmensch
H H
HH
Division of Clinical Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania.
Vlasses
P H
PH
Feinberg
J A
JA
Abrams
W B
WB
Ferguson
R K
RK
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D004311:Double-Blind Method; D005385:Fingers / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism; D013999:Timolol / Q000494:pharmacology*; D014202:Tremor
D000319:Adrenergic beta-Antagonists; D013999:Timolol; D007545:Isoproterenol