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 A(1) adenosine receptor agonists (R)-phenylisopropyladenosine (R-PIA) and N-6-cyclohexyladenosine (CHA) on intraocular pressure (IOP), aqueous humor now (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 mu g) or CHA (20-500 mu g) 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 A(2) antagonist 3.7-dimethyl-1-propargylxanthine (DMPX, 320 mu g) inhibited the early hypertension, without influencing the hypotension. Neither 100 mu g R-PIA nor 500 mu g CHA clearly altered AHF. Total outflow facility was increased by 71% 3 hr after 100 mu g R-PIA, In conclusion, the early ocular hypertension produced by topical adenosine agonists in cynomolgus monkeys is associated with the activation of adenosine A(2) receptors, while the subsequent hypotension appears to be mediated by adenosine A(1) receptors and results primarily from increased outflow facility. (C) 1997 Academic Press Limited.