Abstract
Abstract: :
Introduction: Systemically administered cannabinoids lower intraocular pressure (IOP), but cause undesirable cardiovascular and CNS effects. This study examined the efficacy of topical Win55 212–2, a synthetic cannabinoid, in a model of ocular hypertension. Methods: 3 of 4 episcleral veins were ligated in Sprague–Dawley (n=20) and Long Evans (n=12) rats. After 4–6 wk, by Tonopen® or Goldmann tonometry IOP elevation was > 5 mm Hg. Blood pressure (BP), heart rate (HR), and IOP were measured at baseline, and 30, 60, 90, 120 min after topical instillation (20 uL) of Win55 212–2 (1, 0.5, 0.25, 0.125%) or timolol (0.5%). In other experiments, 50 ug/20 uL of SR141716, a CB1 (cannabinoid receptor) antagonist, was administered topically 30 min before Win55 212–2. Analysis for ocular irritation was performed by slit lamp examination (SLE) at baseline and 120 min.
Results: TocrisolveTM (Win55 212–2 vehicle) alone did not alter IOP. Baseline IOP was 16.8±0.5 mmHg in the operated eye; BP = 126±3/99±2mm Hg; HR = 434±12. Win55 212–2, even at 1%, had no effect on BP or HR. Win55 212–2 (1–0.125%) decreased IOP (p<0.001). After SR141716, Win55 212–2 (1%) decreased IOP by only 1.8±0.9 mmHg versus 8.3±0.7 mmHg with Win55 212–2 alone (p<0.001). SR141716 alone had no effect on IOP. SLE at 120 min noted mild superficial punctate keratitis OU, associated with repeated applanation. Win55 212–2 had no effect on the other eye. In conscious Long Evans rats, Win55 212–2 (1%) reduced IOP from 33.4±1.3 to 24.3±1.3 at 60 min and persisted >120 min. Conclusions: In an ocular hypertensive model topically applied Win55 212–2 is an effective and non–toxic ocular hypotensive agent at concentrations as low as 0.125%. There were no effects on HR or BP, such as those associated with systemic administration. Effects of Win55 212–2 were reversed by the CB1 antagonist, SR141716. The effect of Win55 212–2 was similar to that of 0.5% timolol but of longer duration. Efficacy of Win55 212–2 was demonstrated in two rat strains and was independent of sedation.
Keywords: intraocular pressure • drug toxicity/drug effects • receptors: pharmacology/physiology