Bronchial beta-adrenoceptor blockade following eyedrops of timolol and its isomer L-714,465 in normal subjects.
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.
Richards
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Tattersfield
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D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000097:blood; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D008176:Lung Volume Measurements; D009883:Ophthalmic Solutions; D013999:Timolol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D014786:Vision Disorders / Q000139:chemically induced
D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D013999:Timolol; D007545:Isoproterenol