title: Metipranolol attenuates lipid peroxidation in rat brain: a comparative study with other antiglaucoma drugs.
abstract: 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.
  
  
  CONCLUSIONS
  These data indicate that metipranolol and desacetylmetipranolol exhibit remarkable antioxidant properties, with an effect not dissimilar from the reference antioxidant trolox.
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford, OX2 6AW, UK.
authors.forename: José
authors.initials: J
authors.lastname: Melena
authors.forename: Neville N
authors.initials: NN
authors.lastname: Osborne
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D014290:Metipranolol / Q000494:pharmacology*; D009599:Nitroprusside / Q000633:toxicity; D009883:Ophthalmic Solutions; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D000975:Antioxidants; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D009883:Ophthalmic Solutions; D017392:Thiobarbituric Acid Reactive Substances; D009599:Nitroprusside; D001205:Ascorbic Acid; C029451:ferrous chloride; D014290:Metipranolol