Rotmensch H H, Vlasses P H, Feinberg J A, Abrams W B, Ferguson R K
Division of Clinical Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania.
J Clin Pharmacol. 1993 Jun;33(6):544-8. doi: 10.1002/j.1552-4604.1993.tb04701.x.
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.
在动物中，噻吗洛尔的R-对映体可显著降低眼压，但在外眼受体处的活性仅为S-对映体的1/80。在两组健康男性中进行了一项双盲安慰剂对照试验，比较口服R-和S-噻吗洛尔的β1和β2肾上腺素能受体阻断特性。A组（n = 6）的每位受试者随机接受安慰剂、1 mg和3 mg的S-噻吗洛尔以及25 mg和75 mg的R-噻吗洛尔，B组（n = 5）接受安慰剂、0.5 mg和1 mg的S-噻吗洛尔以及3 mg和10 mg的R-噻吗洛尔。与安慰剂相比，在两组中，R-和S-噻吗洛尔均可同等程度地抑制异丙肾上腺素引起的心率增加（P < .05）、前臂血流量增加（P < .05，但B组在给予R-剂量后，异丙肾上腺素剂量为3微克/分钟时除外）以及手指震颤（P < .05）。基于动物研究和先前的研究，本研究中R-对映体的结果出乎意料，先前的研究表明其他β受体阻滞剂的β阻断作用存在显著差异，其中R-对映体的抑制作用较小。
