title: Effect of lomerizine, a new Ca(2+)channel blocker, on the microcirculation in the optic nerve head in conscious rabbits: a study using a laser speckle technique.
abstract: We examined the effect of a new Ca(2+)channel blocker, lomerizine (KB-2796), and compared it with that of nilvadipine, on the optic nerve head circulation in conscious rabbits using a laser speckle method. Lomerizine (0.03, 0.1 and 0.3 mg kg(-1), i.v.) and nilvadipine (0.003, 0.01 and 0.03 mg kg(-1), i.v.) each significantly increased the normalized blur values (an index of tissue blood velocity) in the optic nerve head in a dose-dependent manner. Neither lomerizine nor nilvadipine caused a significant change in intraocular pressure. Lomerizine produced no significant change in mean arterial blood pressure, although at 0.3 mg kg(-1), i. v. heart rate was significantly increased 5 min after its administration. In contrast, nilvadipine significantly decreased mean arterial blood pressure at 5 to 15 min after its administration and increased heart rate at 5-30 min after its administration (both effects being dose-dependent). Our results indicate that while lomerizine, like nilvadipine, increased tissue blood velocity in the optic nerve head, it did not affect mean arterial blood pressure at the doses that affected optic nerve head circulation, unlike nilvadipine. The plasma concentration of lomerizine (free base) obtained from rabbits at 15 min after administration at a dose of 0. 03 mg kg(-1)i.v., when time there was a significant increase in tissue blood velocity in the optic nerve head, was very similar to plasma concentration with healthy subjects receiving lomerizine at 10 mg (5 mgx2) day(-1), p.o., a dose that achieved a significant reduction in the frequency and mean duration of headache attacks but did not affect the blood pressure or heart rate. These results suggest that lomerizine may be clinically effective in favorably affecting the optic nerve circulation without producing systemic effects such as the hypotension seen during treatment with other Ca(2+)channel blockers.
authors.affiliation: Department of Ophthalmology, Osaka Medical College, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimazawa
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: I
authors.initials: I
authors.lastname: Azuma
authors.forename: M
authors.initials: M
authors.lastname: Araie
authors.forename: Y
authors.initials: Y
authors.lastname: Iwakura
authors.forename: M
authors.initials: M
authors.lastname: Watari
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: H
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology*; D003243:Consciousness; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure; D007834:Lasers; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009898:Optic Disk / Q000098:blood supply*; D010879:Piperazines / Q000097:blood / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D002121:Calcium Channel Blockers; D010879:Piperazines; C035100:nilvadipine; C052424:lomerizine; D009543:Nifedipine