Relationship between nitric oxide production and choroidal blood flow.
OBJECTIVE
To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO).


METHODS
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.


CONCLUSIONS
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.
Xuan
Bo
B
Institute of Ocular Pharmacology and Department of Medical Pharmacology and Toxicology, Texas A & M University System Health Science Center, College Station 77843, USA.
Xu
Xin-Rong
XR
Chiou
George C Y
GC
Zhang
Yi-Hua
YH
Peng
Si-Xun
SX
D000818:Animals; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply / Q000187:drug effects*; D002924:Ciliary Body / Q000098:blood supply; D066298:In Vitro Techniques; D007498:Iris / Q000098:blood supply; D009569:Nitric Oxide / Q000096:biosynthesis*; D009798:Ocular Hypertension / Q000503:physiopathology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism; D013890:Thiourea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
C480782:1-phenyl-3-(3-methoxy-2-propoxy-5-(4-(3,4,5-trimethoxyphenyl)-1,3-dithiolane-2-yl)phenyl)thiourea; D009569:Nitric Oxide; D013890:Thiourea