dinoprost 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

The stainless steel cannula inserting method was used to observe vascular effects of alpha-adrenoceptor agonists, phenylephrine (PE), methoxamine (ME), clonidine (CL) and xylazine (XY), on the isolated, perfused rabbit common carotid, renal and femoral arteries. PE and ME induced a dose-dependent vasoconstriction that was readily suppressed by treatment with bunazosin, an alpha 1-adrenoceptor blocker. CL induced a constriction only in common carotid arteries, and this was readily suppressed by bunazosin. In preparations preconstricted by phenylephrine, CL and XY dose-dependently induced vasodilations in the 3 types of arteries, and these vasodilations were not modified by a potent alpha 2-adrenoceptor antagonist, midaglizole. In preparations preconstricted by prostaglandin F2 alpha, CL and and XY did not produce any significant vasodilation, but CL induced a vasoconstriction in common carotid arteries that was completely blocked by bunazosin. Thus, it is concluded that: 1) alpha 1-adrenoceptors are functionally predominant in rabbit peripheral arteries, 2) the alpha 2-adrenoceptor agonist-induced vasodilation may be due to an antagonistic action towards alpha 1-mediated constrictions, and 3) clonidine has alpha 1-adrenoceptor stimulating properties in rabbit common carotid artery but not in renal and femoral arteries.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Carotid Arteries; Dinoprost; Dose-Response Relationship, Drug; Drug Interactions; Female; Femoral Artery; In Vitro Techniques; Male; Phenylephrine; Quinazolines; Rabbits; Renal Artery; Vasoconstriction

Topics: Adolescent; Adrenergic alpha-Antagonists; Adult; Aged; Asthma; Dinoprost; Female; Humans; Male; Metaproterenol; Middle Aged; Prostaglandins F; Quinazolines