Intraocular pressure responses to the adenosine agonist cyclohexyladenosine: evidence for a dual mechanism of action.
OBJECTIVE
Previous studies have shown that adenosine agonists are effective in reducing intraocular pressure (IOP). However, the mechanism(s) responsible for this ocular hypotensive effect has not been established. This study evaluates the relative contribution of changes in aqueous flow and outflow facility associated with the ocular hypotensive response to the adenosine agonist cyclohexyladenosine (CHA).


METHODS
New Zealand White rabbits were treated topically in one eye with the adenosine A(1) agonist CHA. Changes in IOP, aqueous flow, and total outflow facility at various times after CHA administration were then determined.


RESULTS
These studies demonstrated that CHA produces a dose-related reduction in IOP. Analysis of the dose-response curve revealed an ED(50) and a Hill coefficient of 87 microg and 1.9, respectively. Aqueous flow measurements demonstrated that 1.5 hours after CHA administration, aqueous flow was reduced by 35%. However, by 3.5 hours postdrug, no significant change in aqueous flow was observed. Measurement of the outflow facility found no significant change in facility 1.5 hours after CHA administration. However, by 3.5 hours after CHA administration, outflow facility was significantly increased by 85%.


CONCLUSIONS
These data demonstrate that the adenosine agonist CHA lowers IOP in a dose-related fashion. This hypotensive action results from an early reduction in aqueous flow followed by a subsequent increase in outflow facility. This dual mechanism of action is consistent with analysis of CHA dose-response curve, which indicates that the reduction in IOP induced this agonist's results from multiple mechanisms of action.
Crosson
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Ola B. Williams Glaucoma Therapeutic Development Center, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29425, USA. crossonc@musc.edu
D000241:Adenosine / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015590:Fluorophotometry; D007429:Intraocular Pressure / Q000187:drug effects*; D015814:Ocular Hypotension / Q000139:chemically induced; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits
D058906:Purinergic P1 Receptor Agonists; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine