A New Angiotensin-Ll- Receptor Blocker, Cgp 48933: Local Tolerance and Effect on Intraocular Pressure. A Pilot Study

Abstract

CGP 48933, a new angiotensin-II-receptor antagonist, has been shown to lower intraocular pressure (IOP) in two different rabbit glaucoma models in a dose-dependent manner after local application. As a further step a pilot study was performed in human eyes. The trial consisted of three parts. Parts 1 and 2 comprised a double-masked intraindividual trial between CGP 48933 and its vehicle (saline) in five healthy volunteers (Part 1) and five patients with early stages of primary open-angle glaucoma (Part 2), to assess local tolerance and the effect on IOP. Part 3 was a single-masked intraindividual trial between CGP 48933 and saline, to find the effective dose range of the new compound. Local tolerance was assessed as excellent in all subjects. No conjunctival hyperemia burning or itching occurred. There were no significant changes in IOP from baseline in drug or vehicle-treated eyes. In addition, there was no dose-dependent (200 micrograms to 1 mg) effect of CGP 48933 on IOP. Systemic blood pressure, heart rate and pupil size did not change during the observation period. Topical application of CGP 48933 in its present formulation is thus not suitable for lowering IOP in humans.

Pathophysiologic Implications of Angiotensin I-Converting Enzyme as a Mechanosensor: Diabetes

“…52 The consequence of ACE activation is to decrease the flow across the ciliary epithelium and increase intraocular pressure. [59][60][61][62][63] The mechanism of flow is still not well understood. It is not simple filtration, but appears to involve active transcytosis by mesangial-like cells located within the trabecular meshwork.…”