Effects of adenosine agonists on intraocular pressure and aqueous humor dynamics in cynomolgus monkeys

The effects of single or multiple topical doses of the relatively selective A1 adenosine receptor agonists (R)-phenylisopropyladenosine (R-PIA) and N6-cyclohexyladenosine (CHA) on intraocular pressure (IOP), aqueous humor flow (AHF) and outflow facility were investigated in ocular normotensive cynomolgus monkeys. IOP and AHF were determined, under ketamine anesthesia, by Goldmann applanation tonometry and fluorophotometry, respectively. Total outflow facility was determined by anterior chamber perfusion under pentobarbital anesthesia. A single unilateral topical application of R-PIA (20-250 micrograms) or CHA (20-500 micrograms) produced ocular hypertension (maximum rise = 4.9 or 3.5 mmHg) within 30 min, followed by ocular hypotension (maximum fall = 2.1 or 3.6 mmHg) from 2-6 hr. The relatively selective adenosine A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 320 micrograms) inhibited the early hypertension, without influencing the hypotension. Neither 100 micrograms R-PIA nor 500 micrograms CHA clearly altered AHF. Total outflow facility was increased by 71% 3 hr after 100 micrograms R-PIA. In conclusion, the early ocular hypertension produced by topical adenosine agonists in cynomolgus monkeys is associated with the activation of adenosine A2 receptors, while the subsequent hypotension appears to be mediated by adenosine A1 receptors and results primarily from increased outflow facility.