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K.R. M. Russell, J. Carnes; Morphine–Induced Reduction of Intraocular Pressure: Role of Nitric Oxide . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3671.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the role of nitric oxide in morphine–mediated regulation of intraocular pressure. Methods: IOP was measured in conscious, normal, dark–adapted New Zealand white (NZW) rabbits using a calibrated pneumatonometer. A masked–designed study was conducted in which the rabbits’ eyes were treated with morphine topically and unilaterally; the fellow eyes received vehicle. IOP measurements were taken at 0.5 and 0 hr time before morphine and 0.5, 1, 2, 3, 4 and 5 hr post–treatment. The effect of morphine alone and in the presence of naloxone (non–selective opioid antagonist), L–NAME (nitric oxide synthesis inhibitor), or GSH (morphine sensitive sulfhydryl agent) was determined. Results: Morphine (10, 33, 100 µg/25 µl), produced a concentration–dependent reduction of intraocular pressure. At 0.5 hr post–drug, when compared to the control, morphine significantly reduced IOP from 20.67 ± 0.21 mmHg to 15.67 ± 0.62 mmHg. This was further reduced to 14.92 ± 0.60mmHg at 1.0 hr post–drug. Statistically significant changes in IOP also occurred at 1.0 hr for the 10 and 33 µg/25 µl doses (control – 21.67 ± 0.49 mmHg, 10µg – 17.83 ± 0.61, 33µg – 18.25 ± 0.46 mmHg). The reduction in pressure was maintained throughout the course of the experiment. The reduction of IOP by morphine (100 µg/25 µl) was significantly attenuated in the presence of naloxone (100 µg/25 µl), L–NAME (0.5 %) and GSH (100 µg/25 µl). Conclusions: Based on these results, morphine–induced ocular hypotension is an opioid receptor–mediated response that is sensitive to inhibition of nitric oxide production. Results from this study suggest that agents which augment nitric oxide synthesis could be used in combination with morphine as an alternate treatment in glaucoma therapy.
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