Ocular distribution after topical instillation and potential neuroprotective effect after intravitreal injection of the calcium channel blocker iganipidine.
OBJECTIVE
To investigate the effects of iganidipine, a new calcium antagonist on glutamate agonist-induced retinal damage.


METHODS
Iganidipine was injected with N-methyl-D-aspartate (NMDA) or kainic acid (KA) into the rat vitreous, and the retina was histologically examined. After co-injection with KA, the number of DiI-labeled retinal ganglion cells was also counted. Rabbits received unilateral instillation of 0.03% iganidipine twice daily for 14 days, and the iganidipine level in the posterior retina-choroid was determined by liquid chromatography/mass spectrometry.


RESULTS
Coadministration of iganidipine had no significant effect on NMDA-induced thinning of the inner plexiform layer but partly suppressed KA-induced thinning at final intravitreous concentrations of 10(-8) M or higher, which was confirmed by counting the ganglion cell number. The iganidipine level in the posterior retina-choroid was approximately 6.2 x 10(-7) M in the instilled eye, which was higher than on the contralateral side by 5.2 x 10(-7) M (p = 0.035).


CONCLUSIONS
Iganidipine suppressed KA-induced retinal damage in rats. This suppression was achieved with a lower concentration than that resulting from unilateral instillations of iganidipine in the ipsilateral posterior retina-choroid in rabbits.
Ohashi
Masaaki
M
Eye Clinic, Tokyo Metropolitan Geriatric Medical Center, Tokyo 173-0015, Japan. ohashi.masaaki@nifty.ne.jp
Saito
Shinichiro
S
Fukaya
Yasuhiro
Y
Tomidokoro
Atsuo
A
Araie
Makoto
M
Kashwagi
Kenji
K
Suzuki
Yasuyuki
Y
D000287:Administration, Topical; D000818:Animals; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002452:Cell Count; D002829:Choroid / Q000187:drug effects / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007267:Injections; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology; D010879:Piperazines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000166:cytology; D014018:Tissue Distribution; D014822:Vitreous Body
D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D010879:Piperazines; D011725:Pyridines; D016202:N-Methylaspartate; C108540:iganidipine; D007608:Kainic Acid