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Intraocular Pressure Responses to the Adenosine Agonist Cyclohexyladenosine: Evidence for a Dual Mechanism of Action

From the Ola B. Williams Glaucoma Therapeutic Development Center, Storm Eye Institute, Medical University of South Carolina, Charleston.

PURPOSE. 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 A₁ 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 ED₅₀ and a Hill coefficient of 87 µg 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.

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