Relationship between nitric oxide production and choroidal blood flow.

Purpose: To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO).

Method: Cell culture was used for in vitro experiments to determine the production of NO by NO donors and colored microsphere technique was used for in vivo experiments to determine the blood flow in various tissues of rabbit eyes.

Results: ZX-5 and ZX-4 are two geographic isomers with ZX-5 as trans-form and ZX-4 as cis-form. (1-phenyl-3-[3-methoxy-2-propoxy-5-[4-(3,4,5-trimethoxy-phenyl)-1,3-d lane-2-yl]phenyl]thiourea). It was found that ZX-5 released significant amount of NO at 3, 10, 30 microg/ml concentrations and increased choroid blood flow at 1%, 50 microl instillation into eyes. It was not effective on the blood flow of iris or ciliary body. The corresponding ZX-4 was not effective on ocular blood flow nor it released NO.

Conclusion: ZX-5 can specifically increase the choroidal blood flow which could be useful to suppress the choroidal neovascularization in age-related macular degeneration (AMD). It is hoped that ZX-5 type of compounds could be used for the treatment/prevention of AMD in the elderly.