Central imidazoline (I-1) receptors modulate aqueous hydrodynamics

The purpose of this work is to determine the relative contributions of cent ral imidazoline (I-1) receptors to the ocular hydrodynamic action of moxoni dine. Moxonidine (MOX), an alpha (2) and I-1 receptor agonist, and efaroxan (EFA), a relatively selective I-1 antagonist, were utilized to study alter ations in intraocular pressure (IOP) and aqueous flow in New Zealand white rabbits subjected to intracerebroventricular (i.c.v.) cannulation and sympa thectomy. Intracerebroventricular administration of MOX (0.033, 0.33 and 3. 33 mug) to normal rabbits produced dose-dependent, bilateral IOP decreases of 3, 6, and 8 mmHg, respectively. The ocular hypotensive response to MOX w as immediate (10 min. post drug), lasted for one hour, and was inhibited by prior administration of efaroxan (3.33 mug icv). In unilaterally sympathec tomized (SX) rabbits, the ocular hypotensive response induced by i.c.v MOX in the denervated eye was attenuated approximately 50%, but the duration of ocular hypotension in the surgically altered eye was longer than that of t he normal eye. MOX (0.33 mug icv), caused a statistically significant decre ase (2.24 to 1.59ml/min.) in aqueous flow in normal eyes. In SX eyes, there was no change in aqueous flow by MOX, suggesting that IOP effect in icv MO X observed in the SX eye might be mediated by changes in outflow resistance . Sedation was observed in all the rabbits treated with MOX (icv) and was d ose-dependent. These in vivo data support the suggestion that centrally loc ated I-1 receptors modulate the early contralateral response to topically a dministered MOX and are involved in lowering of IOP and aqueous flow in rab bit. In addition, expression of the fall ocular hypotensive effect of centr ally applied MOX depends on intact sympathetic innervation. Ocular hypotens ion induced by MOX in the SX eye may involve an effect on uveoscleral outfl ow.