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Abstract #15788 Published in IGR 2-3
Ocular effects associated with the chronic administration of the adenosine A(1) agonist cyclohexyladenosine
Crosson CE; Niazi ZCurrent Eye Research 2000; 21: 808-813
PURPOSE: To investigate changes in ocular responses associated with the chronic administration of the adenosine A(1) agonist cyclohexyladenosine (CHA). METHODS: New Zealand White rabbits were treated unilaterally twice a day for 30 days with CHA (165 or 500 μg) or vehicle. Intraocular pressures (IOPs) and pupil diameters (PDs) were evaluated over the course of the study. At the end of the study period, outflow facility was determined in selected animals and compared to naive vehicle- and CHA-treated animals. RESULTS: In rabbits receiving 165 μg of CHA, ipsilateral IOPs at two and six hours post-drug exhibited progressively greater reduction over the course of the study. Regression analysis demonstrated a significant correlation between study duration and lower IOP at two and six hours post-drug. In rabbits receiving 500 μg of CHA, ipsilateral IOP reductions at two hours post-drug were similar throughout the 30-day study. However, analysis of ipsilateral IOPs six hours following CHA administration, demonstrated a significant correlation between study duration and lower IOPs. Enhanced contralateral responses at two hours post-drug, were also measured in rabbits receiving 165 or 500 μg of CHA. In animals receiving chronic CHA treatment for 30 days, outflow facility three hours post-CHA was significantly elevated over that measured in naive vehicle-treated rabbits. Although mean outflow facility in chronic treatment animals was slightly elevated over CHA-induced increases in naive rabbits, this difference was not significant. No evidence of tolerance was observed for either dose during the course of these studies. No change in PD during the course of these studies was measured. CONCLUSIONS: The chronic administration of the adenosine A(1) agonist CHA twice daily produced no evidence of tolerance. Unexpectedly, the IOP response to CHA was enhanced with chronic administration. These data provide evidence that the use of adenosine A(1) agonists may be useful in the chronic treatment of ocular hypertension at doses lower than those identified in acute IOP studies.
Dr. C.E. Crosson, Department of Ophthalmology and Visual Sciences, Texas Technical University Health Sciences Center, Lubbock, TX, USA
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
