title: Neuroprotective effect of the novel Na+/Ca2+ channel blocker NS-7 on rat retinal ganglion cells.
abstract: OBJECTIVE
  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.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan. saito@nms.ac.jp
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Saito
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ohashi
authors.forename: Akira
authors.initials: A
authors.lastname: Naito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fukaya
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004596:Electroretinography; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000503:physiopathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D011743:Pyrimidines; D026941:Sodium Channel Blockers