Effects of lomerizine, a novel Ca2+ channel blocker, on the normal and endothelin-1-disturbed circulation in the optic nerve head of rabbits.
We examined the effects of lomerizine, a new diphenylmethylpiperazine Ca2+ channel blocker, on the normal circulation in the optic nerve head and long posterior ciliary artery, and on endothelin-1-induced hypoperfusion in the optic nerve head in anesthetized rabbits using a hydrogen gas clearance method and laser Doppler flowmetry. These effects were compared with those of nilvadipine and pranidipine. Lomerizine (0.1 and 0.3 mg/kg, i.v.) significantly increased tissue blood flow in the optic nerve head and the putative blood flow in the long posterior ciliary artery with smaller reduction of blood pressure (0.3 mg/kg, i.v.) and without change in heart rate. On the other hand, nilvadipine (0.003 and 0.01 mg/kg, i.v.) and pranidipine (0.003 and 0.01 mg/kg, iv.) each significantly increased blood flow and lowered blood pressure. Moreover, lomerizine (0.1 and 0.3 mg/kg, i.v.) and nilvadipine (0.01 mg/kg, i.v.), when administered 5 min before an endothelin-1 injection (10(-6) M, 100 microl), inhibited the hypoperfusion in the optic nerve head. These results suggest that lomerizine improves the ocular circulation with minimal cardiovascular side effects. Therefore, lomerizine may have clinical potential for the treatment of eye diseases associated with local circulatory disturbances, such as normal-tension glaucoma.
Toriu
N
N
Pharmacology Group, R&D Laboratories, Nippon Organon K.K., Osaka, Japan. t_nobuko@f7.dion.ne.jp
Sasaoka
M
M
Shimazawa
M
M
Sugiyama
T
T
Hara
H
H
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019842:Ciliary Arteries / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D007429:Intraocular Pressure / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009898:Optic Disk / Q000098:blood supply*; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019332:Endothelin-1; D010879:Piperazines; C035100:nilvadipine; C048161:pranidipine; C052424:lomerizine; D009543:Nifedipine