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Kevin M. Bowman, Sandeep S. Samudre, Ben Mandel, Alireza Hosseini, Patricia B. Williams, Frank A. Lattanzio, Jr.; β-adrenergic Antagonists, Carbonic Anhydrase Inhibitors And α2-agonists Reduce The Effects Of Cannabinoids In A Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3101.
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Topically applied endocannabinoid analogs have been reported to reduce intraocular pressure (IOP). Combination of timolol, a β-adrenergic antagonist and dorzolamide, a carbonic anhydrase inhibitor, decreases IOP more than either drug alone. In this study, the endocannabinoid analog, O-1812, was combined with timolol, dorzolamide, or brimonidine, an α2-agonist, to evaluate the effect of the combination on IOP in a rat glaucoma model.
Surgical ligation of 3 of the 4 episcleral veins in eyes of Sprague Dawley rats caused a lasting IOP increase. IOP was measured by Tonolab at baseline and at 30, 60 and 120 min. Each drug was applied alone or in combination with O-1812. For combination therapy, following baseline IOP, timolol 0.5%, brimonidine 0.2% or dorzolamide 2.0% were applied topically followed 10 min later by O-1812 1.0%. Analysis for ocular irritation was performed at slit lamp at baseline and at 120 min. Results are reported as a percentage of baseline.
Within 30 min all drugs and combinations significantly decreased IOP compared to baseline (p<0.05). Among single drug regimens O-1812 and dorzolamide provided the largest reduction (p<0.05). Yet, when O-1812 was combined with timolol or dorzolamide, IOP was significantly greater than either drug alone (p<0.05). When O-1812 was combined with brimonidine, reduction in IOP was greater than brimonidine alone, but not different from O-1812 alone. No drug alone or in combination caused ocular irritation or systemic effects.
Combination of cannabinoids with β-adrenergic antagonist or carbonic anhydrase inhibitor reduced the effect of cannabinoid. Although cannabinoids reduce IOP primarily through CB1 receptor, it could be postulated that further downstream signalling events depend on cross reactivity between β-adrenergic receptors and carbonic anhydrase inhibitors.
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