Different neurorescue profiles of selegiline and p-fluoro-selegiline in gerbils.
The neuroprotective/neuronal rescue effects of selegiline are not exactly understood, and show great variability in clinical trials. In this study, the dose-dependence of neuronal rescue potency of selegiline and its analogue para-fluoro-selegiline (PFS) was investigated in gerbils. The compounds were tested in a transient global cerebral ischemia model. Selegiline expressed a bell-shaped, dose-response curve with high intrinsic activity (with greatest effect at 0.001 mg/kg), as opposed to PFS which shows a saturation profile. These findings indicate possible therapeutic differences between PFS and selegiline in the treatment of neurodegenerative disorders. Inhibition of progression of the disease (neuroprotective effect) and improvements of symptoms (MAO-B inhibition) may occur at the same dose level using PFS, while these doses are separated in case of selegiline.
Erdö
F
F
Discovery Research Department, Sanofi-Synthelabo-CHINOIN Pharmaceutical and Chemical Works Co. Ltd., Budapest, Hungary.
Baranyi
A
A
Takács
J
J
Arányi
P
P
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D017611:Fluorine Compounds / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D012642:Selegiline / Q000031:analogs & derivatives / Q000494:pharmacology*
D017611:Fluorine Compounds; D018696:Neuroprotective Agents; D012642:Selegiline