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K. Pratap, F.A. Lattanzio, Jr., R.C. Allen, P. Loose–Thurman, E.R. Crouch, Jr.; In Normal Rabbits, Topical WIN–55–212–2 Decreases IOP Without Effect on Heart Rate and Blood Pressure . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2098.
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Purpose:While cannabinoids are known to decrease IOP, current systemic treatment methods result in undesired effects. Alternatively, topical application of cannabinoids may decrease IOP and eliminate systemic effects. Topical application of WIN–55–212–2, a nonspecific cannabinoid agonist, in TocrisolveTM, a new diluent specific for cannabinoids, was studied. Methods: WIN–55–212–2 (0.125%, 0.25%, 0.5%, and 1.0% w/v) or TocrisolveTM alone was topically administered to New Zealand rabbits. IOP, blood pressure (BP) and heart rate (HR) were measured at baseline and at 30, 60, and 120 minutes. IOP was recorded using pneumotonometry (Mentor, Norwell, MA) and BP and HR using a tail cuff and analyzed by DasyLab software (DasyTEC, Amherst, NH). In other experiments, 25µg/µl of SR171416, a CB1 antagonist, or SR144528, a CB2 antagonist, were applied topically 30 min before WIN –55–2112 (1.0%). Results: WIN–55–212–2 (1.0%) significantly reduced IOP from baseline (20.53±3.49 mmHg) to 17.22±2.67 mmHg at 30min (p=0.003) and to19.43±1.66 mmHg at 60min (p=0.006). WIN–55–212–2 (0.5%) also significantly reduced IOP from 18.63±3.58 to 17.085±3.14 (p=0.004) at 30min and to 16.92±3.32 at 60min (p<0.001). Lower concentrations did not show significant effects. WIN–55–212–2 (0.5%) had no effect on the HR (p= 0.960), unlike IV WIN–55–212–2 (0.1mg/kg). which significantly decreased both HR and BP. Likewise, treatment with TocrisolveTM alone, the control, did not affect HR. BP and HR were not significantly affected by any topical treatments. CB1 and CB2 antagonists had marginal effects (p>0.05). Conclusions: This research suggests that cannabinoids, administered topically, can lower IOP while minimizing systemic effects. It is not possible to verify whether WIN–55–212–2 decreased IOP through action at CB–1 or CB–2 receptors until higher concentrations can be studied.
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