uf-021 and bunazosin

Recently, an epidemiological study was conducted in Japan by Shiose, et al, and the prevalence of open-angle glaucoma in Japanese aged 40 years or older was found to be 2.62% [primary open-angle glaucoma 0.58%, low-tension glaucoma (LTG) 2.04%]. Historically, treatment for glaucoma has been based on lowering intraocular pressure. It is also necessary to improve intraocular blood flow. In the beginning of the study, the effect of anti-glaucoma agents on choroidal blood flow was examined in rabbit eyes. An increase of choroidal blood flow was found following topical application of the prostaglandin-related compound isopropyl unoprostone (UF-021) and the adrenergic alpha-1 antagonist bunazosin hydrochloride (DE-070). Then, a new vasoconstrictor, endothelin, showed strong effects on intraocular pressure, intraocular circulation, and visual function in rabbit eyes. Endothelin-1 (ET-1) was found to be a marked vasoconstrictor with prolonged reduction of intraocular pressure and the blood flow in the choroid and optic nerve head. The effects were suppressed by Ca2+ channel blocker and adrenergic alpha-1 blocker. Plasma concentration of ET-1 was determined by radioimmunoassay in patients with glaucoma. A significantly high level of ET-1 concentration was seen in patients with LTG. Endothelin appears to be an important tool for studying the pathogenesis of LTG. Finally, a prospective clinical trial of the therapeutic effects of bunazosin hydrochloride was performed in patients with LTG for one year. Clinical usefulness was evaluated by changes in the mean deviation value of Humphrey perimetry. Satisfactory results were obtained in maintaining the visual field and in reducing intraocular pressure. In the light of our investigations, it is advisable to introduce an adrenergic alpha-1 blocker or prostaglandin-related compound for reduction of glaucomatous damages. We look forward to the development of the neuro-protective future glaucoma therapy.

Topics: Adrenergic alpha-Antagonists; Choroid; Dinoprost; Endothelins; Glaucoma; Humans; Intraocular Pressure; Ophthalmic Solutions; Quinazolines; Regional Blood Flow