The neuroimmunophilin GPI-1046 partially protects against 3-acetylpyridine toxicity in the rat.
There are no published reports assessing whether the non-immunosuppressant immunophilin ligand GPI-1046, which has putative neurotrophic effects in a variety of models of neurotoxicity, possesses neuroprotective effects in the 3-acetylpyridine (3AP) toxicity model in rats. The purpose of the present study was to assess whether 3AP toxicity is mitigated by administration of GPI-1046. Survival after 3AP challenge and licking performance in surviving rats were used to measure the beneficial effects of GPI-1046. GPI-1046 increased animal survivability and partially ameliorated 3AP-induced performance deficits at the lick task when GPI-1046 was administered concurrently with a peri-lethal dose of 3AP (50 mg/kg).
Moss
Sheldon J
SJ
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045, USA.
Birkestrand
Brenda
B
Fowler
Stephen C
SC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
C104949:GPI 1046; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011725:Pyridines; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; C010835:3-acetylpyridine; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase