Effects of Ibuterol, a β-2 Adrenergic Prodrug, on Intraocular Pressure

Abstract

Ibuterol, a prodrug of terbutaline, was approximately 100 times more potent than terbutaline in producing ocular hypotension in the treated eye of normal and sympathectomized (SX) rabbits. In normal rabbits, ibuterol produced no change in IOP of the contralateral eye whereas in unilaterally SX rabbits a rise in IOP occurred in the SX (contralateral) eye when the normal eye was treated with ibuterol.Ibuterol also suppressed ocular hypertension induced by water loading and delayed the IOP recovery rate although its onset of action was delayed. Aqueous flow was increased significantly at 1 hr after ibuterol in fluorophotometric studies in normal rabbits. Pretreatment with forskolin antagonized rather than enhanced ibuterol-induced ocular hypotension. Pretreatment with diclofenac failed to suppress the development of tachyphylaxis to the ocular hypotensive effect of ibuterol. Although ibuterol is an effective ocular hypotensive agent in rabbits, the effects of this agent on aqueous flow are complex and tachyphylaxis to the ocular hypotensive effect develops fairly rapidly.

Effect of the Antiglaucoma Agent JV-GL1 and Related Compounds in the Canine Eye

“…Antiglaucoma agents that use the cAMP/PKA pathway as an intracellular signal transduction pathway, such as b 2adrenoceptor agonists, tend to develop tachyphylaxis. 11 This results in a rapid loss of ocular hypotensive activity. The free acid product of JV-GL1 enzymatic hydrolysis, PGN 9856, potently increased cAMP levels in human EP 2 receptor transfected cells.…”