A single dose of three different ophthalmic beta-blockers antagonizes the chronotropic effect of isoproterenol in healthy volunteers

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Abstract
The systemic effect of three .beta.-blocking eyedrops was compared in a placebo-controlled, double-blind trial in 12 healthy male volunteers. Each subject received successively each treatment in random order at weekly intervals. The eyedrops administered were as follows: 0.5% timolol, 2% carteolol, 0.6% metipranolol, and placebo. We evaluated the intraocular pressure and systemic .beta.-blockade 3 hours after a single administration of one eyedrop in each eye. The systemic .beta.-blocking effect was evaluated by the isoproterenol sensitivity test, that is the dose of isoproterenol required to increase resting heart rate by 25 bpm (I25). Each .beta.-blocking eyedrop antagonized the chronotropic effect of isoproterenol. I25 for placebo was 3.1 .+-. 0.5 .mu.g, for metipranolol 5.2 .+-. 0.9 .mu.g (P < 0.05), for timolol 10.9 .+-. 1.9 .mu.g (P < 0.001), and for carteolol 39.6 .+-. 5.4 .mu.g (P < 0.0005). Each treatment significantly decreased the intraocular pressure: metipranolol 3.6 .+-. 0.4 mm Hg (P < 0.001), timolol 2.44 .+-. 0.4 mm Hg (P < 0.01), and carteolol 2.38 .+-. 0.48 mm Hg (P < 0.01) compared with placebo. The resting heart rate and blood pressure were not influenced by the treatments. Even though the results might be different in the case of an earlier or a latter time of evaluation or chronic administration, we believe that the isoproterenol sensitivity test may be used to evaluate the systemic effect of .beta.-blocking eyedrops.