title: Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx.
abstract: The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45Ca(2+) influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 microM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on [3H]nitrendipine or [3H]diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified.
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Nash
authors.forename: J P
authors.initials: JP
authors.lastname: Wood
authors.forename: J
authors.initials: J
authors.lastname: Melena
authors.forename: N N
authors.initials: NN
authors.lastname: Osborne
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D005333:Fetus; D007511:Ischemia / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D012171:Retinal Vessels / Q000502:physiology / Q000503:physiopathology*; D018800:Thy-1 Antigens / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D016202:N-Methylaspartate; C034161:flupirtine; D002118:Calcium