Effects of beta-blockers association with pilocarpine on rabbit intraocular pressure and heart rate.

The effect of 7-days BID (twice in a day) or TID (three times in a day) administration of the eye-drop combinations of timolol and pilocarpine (0.5% and 2%, respectively), metipranolol and pilocarpine (0.1% and 2%, respectively) or placebo on intraocular pressure (IOP) and heart rate (HR) of conscious rabbits were studied in order to assess the pharmacological potency of the combinations and their heart side effects. TID administration of both pharmacological combinations was followed by similar decrease of IOP as measured over 24 h (at 4.00 and 20.00 h). After the BID administration, a reduction in IOP was observed only twice with the timolol-pilocarpine combination. In contrast, a constant reduction in IOP was seen with the metipranolol-pilocarpine combination. Furthermore, the TID administration of the timolol-pilocarpine combination exerted a decrease of IOP that appeared to be more pronounced than that observed after the BID administration of the same combination, while no difference was found between the TID and BID administration of the metipranolol-pilocarpine treatment. Heart rate, when measured after 7 days of treatment, appeared to be constantly decreased only in the group of animals which received the TID administration of timolol-pilocarpine combination. The present results suggest that the BID or TID administration of metipranolol-pilocarpine combination was fully effective in reducing IOP without influencing HR. The timolol-pilocarpine association appeared to be fully active in reducing IOP only under the TID administration schedule. However, this rate of administration was followed by a constant reduction of HR. Thus, on a dose basis the metipranolol-pilocarpine combination appeared to be more effective in reducing IOP and less effective in inducing bradycardia than the timolol-pilocarpine association.