Ocular effects associated with the chronic administration of the adenosine A(1) agonist cyclohexyladenosine.
OBJECTIVE
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 microg) 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 naïve vehicle- and CHA-treated animals.


RESULTS
In rabbits receiving 165 microg of CHA, ipsilateral IOPs at 2 and 6 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 2 and 6 hours post-drug. In rabbits receiving 500 microg of CHA, ipsilateral IOP reductions at 2 hours post-drug were similar throughout the 30-day study. However, analysis of ipsilateral IOPs 6 hours following CHA administration, demonstrated a significant correlation between study duration and lower IOPs. Enhanced contralateral responses at 2 hours post- drug, were also measured in rabbits receiving 165 or 500 microg of CHA. In animals receiving chronic CHA treatment for 30 days, outflow facility 3 hours post-CHA was significantly elevated over that measured in naïve vehicle-treated rabbits. Although mean outflow facility in chronic treatment animals was slightly elevated over CHA-induced increases in naïve 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.
Crosson
C E
CE
Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. crossonc@musc.edu
Niazi
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D000241:Adenosine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D004361:Drug Tolerance; D007429:Intraocular Pressure / Q000187:drug effects*; D011680:Pupil / Q000187:drug effects*; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits; D012044:Regression Analysis
D058906:Purinergic P1 Receptor Agonists; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine