PURPOSE: To investigate whether NS-7, 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride, a novel Na(+)/Ca(2+) channel blocker, can protect the rat retina subjected to ischemia-reperfusion insult. METHODS: To evaluate the protective effect of NS-7 against retinal damage, the drug was administered before and after ischemia-reperfusion. Damage to the retina was assessed by measuring the thickness of the inner plexiform layer (IPL) and the outer nuclear layer (ONL) of each eye. In a subsequent experiment, electroretinographic (ERG) evaluation was also used. RESULTS: In histopathologic evaluation, ischemia-reperfusion injury caused a significant reduction of IPL thickness (measured as the IPL/ONL ratio). In the NS-7-treated group, retinal damage was partially prevented by a concentration of 0.25 mg/kg per day. In the ERG evaluation, ischemia-reperfusion injury caused a reduction of A- and B-wave amplitudes. NS-7 treatment significantly prevented the reduction of the B wave at a concentration of 0.1 or 0.3 mg/kg, while the reduction of the A wave was not significantly affected. CONCLUSIONS: NS-7 has neuroprotective effects against retinal damage resulting from subjection to ischemia. In addition, NS-7 can be used as an agent for treating acute ischemic retinopathy, including diseases associated with very high intraocular pressure, such as acute angle-closure glaucoma.
PURPOSE: To investigate whether NS-7, 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride, a novel Na(+)/Ca(2+) channel blocker, can protect the rat retina subjected to ischemia-reperfusion insult. METHODS: To evaluate the protective effect of NS-7 against retinal damage, the drug was administered before and after ischemia-reperfusion. Damage to the retina was assessed by measuring the thickness of the inner plexiform layer (IPL) and the outer nuclear layer (ONL) of each eye. In a subsequent experiment, electroretinographic (ERG) evaluation was also used. RESULTS: In histopathologic evaluation, ischemia-reperfusion injury caused a significant reduction of IPL thickness (measured as the IPL/ONL ratio). In the NS-7-treated group, retinal damage was partially prevented by a concentration of 0.25 mg/kg per day. In the ERG evaluation, ischemia-reperfusion injury caused a reduction of A- and B-wave amplitudes. NS-7 treatment significantly prevented the reduction of the B wave at a concentration of 0.1 or 0.3 mg/kg, while the reduction of the A wave was not significantly affected. CONCLUSIONS:NS-7 has neuroprotective effects against retinal damage resulting from subjection to ischemia. In addition, NS-7 can be used as an agent for treating acute ischemic retinopathy, including diseases associated with very high intraocular pressure, such as acute angle-closure glaucoma.
Authors: K Adachi; Y Fujita; C Morizane; A Akaike; M Ueda; M Satoh; H Masai; S Kashii; Y Honda Journal: Eur J Pharmacol Date: 1998-05-29 Impact factor: 4.432