Metipranolol attenuates lipid peroxidation in rat brain: a comparative study with other antiglaucoma drugs

Background: Free radical production seems to be involved in the pathogenesis of a number of ocular diseases. Certain beta-adrenoceptor antagonists display antioxidant properties, but these have not been ascribed to any of the presently used ophthalmic beta-adrenoceptor antagonists. Therefore, we examined the influence of ophthalmic beta-adrenoceptor antagonists and other antiglaucoma drugs on stimulated lipid peroxidation in rat brain homogenates.

Methods: Lipid peroxidation in rat brain homogenates was stimulated by iron/ascorbate or sodium nitroprusside. Lipid peroxidation was assessed by the formation of thiobarbituric acid reactive species (TBARS).

Results: Of the antiglaucoma drugs tested (brimonidine, carteolol, dorzolamide, latanoprost, levobetaxolol, levobunolol, metipranolol, pilocarpine, timolol, travoprost and unoprostone), only metipranolol and its active metabolite, desacetylmetipranolol, were found to significantly reduce iron/ascorbate-induced lipid peroxidation in rat brain homogenates with IC50 values of 6.9 and 1.1 microM, respectively. Metipranolol and desacetylmetipranolol also concentration-dependently inhibited sodium nitroprusside-stimulated lipid peroxidation in rat brain homogenates, displaying IC50 values of 25.1 and 2.6 microM, respectively.

Conclusion: These data indicate that metipranolol and desacetylmetipranolol exhibit remarkable antioxidant properties, with an effect not dissimilar from the reference antioxidant trolox.