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

The systemic effect of three β‐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 β‐blockade 3 hours after a single administration of one eyedrop in each eye. The systemic β‐blocking effect was evaluated by the isoproterenol sensitivity test, that is the dose of isoproterenol required to increase resting heart rate by 25 bpm (I 25 ). Each β‐blocking eyedrop antagonized the chronotropic effect of isoproterenol. I 25 for placebo was 3.1 ± 0.5 μg, for metipranolol 5.2 ± 0.9 μg (P < 0.05), for timolol 10.9 ± 1.9 μg (P < 0.001), and for carteolol 39.6 ± 5.4 μg (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 later time of evaluation or chronic administration, we believe that the isoproterenol sensitivity test may be used to evaluate the systemic effect of β‐blocking eyedrops. Clinical Pharmacology and Therapeutics (1987) 41 , 622–626; doi: 10.1038/clpt.1987.85