Bronchial beta-adrenoceptor blockade following eyedrops of timolol and its isomer L-714,465 in normal subjects

Br J Clin Pharmacol. 1985 Nov;20(5):459-62. doi: 10.1111/j.1365-2125.1985.tb05097.x.

Abstract

The R-enantiomer of timolol, L-714,465, is considerably less potent as a beta 1- and beta 2-adrenoceptor antagonist in animals than timolol, whilst only slightly less potent in reducing intraocular pressure. If the same was true in man L-714,465 would have potential benefits over timolol in the treatment of glaucoma. The extent of bronchial beta-adrenoceptor blockade following one eyedrop in each eye of timolol 1% and L-714,465 1% was compared in six normal subjects, by measuring the displacement of the bronchodilator dose-response curve to isoprenaline following each drug compared to the isoprenaline dose-response curve after placebo eyedrops (methyl-cellulose). There was no significant difference between the dose-response curves to L-714,465 and placebo, but a significant displacement of the dose-response curve following timolol. The geometric mean dose ratio following timolol (21) differed significantly from that following L-714,465 (1.6). Heart rate at the end of the isoprenaline dose-response study was lower after timolol, despite the fact that subjects had received higher doses of isoprenaline. The trend was in the same direction after L-714,465 when compared with placebo though less marked. L-714,465 clearly causes less beta-adrenoceptor blockade than timolol when given as 1% eyedrops. The effects of L-714,465 1% on the airways and heart rate did not differ significantly from placebo in these six subjects but the pattern of response would be most consistent with L-714,465 having some beta-adrenoceptor blocking activity though considerably less than timolol.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists* / adverse effects
  • Adrenergic beta-Antagonists* / blood
  • Adult
  • Arrhythmias, Cardiac / chemically induced
  • Bronchial Provocation Tests
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Humans
  • Isoproterenol / adverse effects
  • Isoproterenol / antagonists & inhibitors
  • Lung Volume Measurements
  • Ophthalmic Solutions
  • Timolol / adverse effects
  • Timolol / blood
  • Timolol / pharmacology*
  • Vision Disorders / chemically induced

Substances

  • Adrenergic beta-Antagonists
  • Ophthalmic Solutions
  • Timolol
  • Isoproterenol