Comparative effects of antiglaucoma drugs on voltage-dependent calcium channels

Background: Experimental evidence suggests that substances able to interact with voltage-dependent Ca2+ channels (VDCCs) might be beneficial in glaucoma management. It was therefore of significance to show that β-adrenoceptor antagonists used in glaucoma directly interact with L-type VDCCs. In the present study, the affinity of several antiglaucoma drugs (betaxolol, carteolol, levobunolol, timolol, brimonidine, dorzolamide, latanoprost and pilocarpine) for these and other VDCCs was investigated using radioligand binding assays. Experiments were also carried out to assess the effect of antiglaucoma drugs on the NMDA-stimulated Ca2+ influx into isolated rat retinas. Methods: Competition radioligand binding studies to L-, N- and P/Q-type VDCCs were performed in rat cortical homogenates. The effects of antiglaucoma drugs on the NMDA-stimulated influx of 45Ca2+ were studied in isolated rat retinas. Results: Only β-adrenoceptor antagonists significantly interacted with radioligand binding to L-type VDCCs, with betaxolol displaying the highest potency. None of the antiglaucoma drugs tested showed any significant affinity for either N- or P/Q-type VDCCs. Only β-adrenoceptor antagonists attenuated the NMDA-stimulated 45Ca2+ influx into isolated rat retinas, with betaxolol exhibiting at least 10 times higher potency than timolol. Brimonidine, dorzolamide, latanoprost and pilocarpine did not elicit any significant effect on the NMDA-stimulated 45Ca2+ influx. Additional experiments strongly suggested that the effect of betaxolol on the NMDA-stimulated 45Ca2+ resulted from inhibition of L-type VDCCs. Conclusion: Of the antiglaucoma drugs investigated, betaxolol displays the greatest L-type VDCC-blocking activity and this may be of clinical relevance. Such a characteristic could account for some of its described ocular actions.