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Additive Effects Of Timolol And Cannabinoids On Intraocular Pressure In A Rat

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Additive Effects of Timolol and Cannabinoids on Intraocular Pressure in a Rat Glaucoma Model

M. H. Oltmanns1, S. S. Samudre1, F. A. Lattanzio, Jr.1, B. R. Martin2, I. G. Castillo2 and P. B. Williams1

1TR Lee Center for Ocular Pharm, Dept. Phys. Sci., Eastern Virginia Medical School, Norfolk, Virginia
2Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia

Commerical Relationships: M.H. Oltmanns, None; S.S. Samudre, None; F.A. Lattanzio, None; B.R. Martin, None; I.G. Castillo, None; P.B. Williams, None.

Support: Supported in part by Richmond Eye & Ear Foundation, Richmond, VA.

Abstract

Purpose:Half of all glaucoma patients cannot be maintained on single drug therapy e.g., timolol alone; most require use of two or even three drugs to control their IOP. Cannabinoids are known to reduce IOP. Since cannabinoids and timolol have different mechanisms of action, there is potential for a synergistic effect. In the present study, we examined the combination of timolol and a synthetic cannabinoid (WIN55 212-2, O-1812, or O-2545) to reduce IOP in a chronic rat model of ocular hypertension.

Methods:Surgical ligation of three of the four episcleral veins in one eye of Sprague Dawley rats caused a long lasting (>44 wk) IOP increase. IOP was measured by Goldmann tonometry at baseline (-30), 0, 30, 60 and 120 min, as was heart rate and blood pressure. For combination therapy, after baseline IOP measurement, timolol 0.5% was applied topically followed 30 min later by WIN55 212-2 1.0%, O-1812 1.0%, or O-2545 1.0%. In another experiment, O-1812 1.0% and O-2545 1.0% were administered simultaneously. An analysis for ocular irritation was performed by slit lamp examination (SLE) at baseline and 150 min.

Results:
Table 1* significantly lower than baseline, p<0.05{dagger} significantly lower than O-1812 1.0% alone, p<0.05{ddagger} significantly lower than O-2545 1.0% alone, p<0.05Within 30 min all combinations significantly decreased IOP. Unlike timolol alone, after the addition of the cannabinoids, IOP reduction was maintained for over 120 min. The combination of O-1812 and O-2545 had the greatest effect. No combination caused ocular irritation or systemic effects.

Conclusions::Compared to timolol alone, combination therapy with timolol and cannabinoids prolonged both the duration and magnitude of their effect on IOP. However, the combination of two synthetic cannabinoids also had synergistic effects. The potential for multidrug therapy using cannabinoids may provide a greater benefit.

Keywords: intraocular pressure - aqueous


Source: Additive Effects of Timolol and Cannabinoids on Intraocular Pressure in a Rat Glaucoma Model
 
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