advertisement
Abstract #20615 Published in IGR 10-1
Topical WIN55212-2 alleviates intraocular hypertension in rats through a CB1 receptor mediated mechanism of action
Oltmanns MH; Samudre SS; Castillo IG; Hosseini A; Lichtman AH; Allen RC; Lattanzio Jr FA; Williams PBJournal of Ocular Pharmacology and Therapeutics 2008; 24: 104-115
INTRODUCTION: Systemically administered cannabinoids can reduce intraocular pressure (IOP), but produce undesirable cardiovascular and central nervous system effects. In a chronic model of ocular hypertension, we examined the efficacy of acute topical administration of WIN55212-2 (WIN) in a novel commercially available vehicle and in combination with timolol. METHODS: IOP was chronically elevated by the surgical ligature of vortex veins in Sprague Dawley rats. IOP was measured by using Goldmann applanation tonometry. IOP, blood pressure (BP), and heart rate (HR) were measured at baseline and 30, 60, 90, and 120 min after the topical administration of WIN 1.0%, 0.25%, 0.06%, or 0.015%, the commercially available vehicle, timolol 0.5%, or a combination of WIN and timolol. SR141716 (CB1 antagonist) or SR144528 (CB2 antagonist) was administered topically 30 min before WIN to determine receptor specificity. To determine ocular and systemic penetration, (3)H WIN 55212-2 was administered topically and tissues were collected at 60 and 120 min. Ocular irritation was evaluated by slit-lamp examination (SLE) at baseline and 120 min. RESULTS: WIN significantly decreased IOP in the hypertensive eye, with no BP or HR effects. SR141716 pretreatment significantly inhibited the IOP effects of WIN 1.0% in a dosedependent manner, while SR 144528 was not as effective. No significant additive effects were observed by combining WIN (0.5% or 1.0%) with timolol 0.5%. WIN was retained in ocular tissue with a t(1/2) of 80-100 min. SLE at 120 min revealed no solvent or drug-related toxic effects. CONCLUSIONS: In a chronic ocular hypertensive rat model, topically applied WIN is an effective, nontoxic ocular hypotensive agent with no hemodynamic side-effects. This effect was predominantly CB1 receptor mediated, but some CB2 contribution could not be ruled out.
Dr. S.S. Samudre, Department of Physiological Sciences, Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501, USA. Sandeepsamudre@gmail.com
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
