Ocular distribution after topical instillation and potential neuroprotective effect after intravitreal injection of the calcium channel blocker iganipidine.

Abstract

PURPOSE:

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.

• Authors: Masaaki Ohashi, Shinichiro Saito, Yasuhiro Fukaya, Atsuo Tomidokoro, Makoto Araie, Kenji Kashwagi, Yasuyuki Suzuki
• Journal: Current eye research (Curr Eye Res) Vol. 30 Issue 4 Pg. 309-17 (Apr 2005) ISSN: 0271-3683 [Print] England
• PMID: 16020261 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Neuroprotective Agents
• Piperazines
• Pyridines
• N-Methylaspartate
• iganidipine
• Kainic Acid

Topics

• Administration, Topical
• Animals
• Calcium Channel Blockers (pharmacokinetics, pharmacology)
• Cell Count
• Choroid (drug effects, metabolism)
• Gas Chromatography-Mass Spectrometry
• Injections
• Kainic Acid (toxicity)
• Male
• N-Methylaspartate (toxicity)
• Neuroprotective Agents (pharmacology)
• Piperazines (pharmacokinetics, pharmacology)
• Pyridines (pharmacokinetics, pharmacology)
• Rats
• Rats, Wistar
• Retina (drug effects, metabolism)
• Retinal Degeneration (chemically induced, pathology, prevention & control)
• Retinal Ganglion Cells (cytology)
• Tissue Distribution
• Vitreous Body