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

Abstract

1 The R-entantiomer 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. 2 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 (methylcellulose). 3 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) 4 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. 5 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.