title: LA-419, a nitric-oxide donor for the treatment of cardiovascular disorders.
abstract: LA-419, currently being developed by Lacer SA, is a thiol-containing analog of isosorbide mononitrate that is undergoing assessment in clinical trials for the treatment of chronic ischemic cardiovascular disorders. The compound was originally designed to have a reduced tendency toward tolerance sensitivity - a major limitation of established organic nitrate compounds. The rationale behind the drug design was to include an antioxidant moiety in the drug structure to combat the contribution of oxidative stress in tolerance induction. The compound is at an early stage of development, but has already provided some surprising data. First, LA-419 does not appear to require the nitroxy ester moiety for activity and its actions might not be mediated only by nitric oxide release. Second, unlike conventional nitrates, LA-419 is active in platelets, suggesting a potential role as an antithrombotic agent. Third, LA-419 has a profound impact on left ventricular hypertrophy, making the drug a plausible candidate for several additional potential therapeutic opportunities. In addition, LA-419 has demonstrated potential in the treatment of glaucoma and intestinal disorders. At the time of publication, LA-419 was in phase II clinical trials in patients with chronic ischemic cardiovascular disorders.
authors.affiliation: UHI Millennium Institute, Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, Centre for Health Science, Inverness, UK. ian.megson@uhi.ac.uk
authors.forename: Ian L
authors.initials: IL
authors.lastname: Megson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Leslie