Tacrine and donepezil attenuate the neurotoxic effect of A beta(25-35) in rat PC12 cells.
The effect of the cholinesterase inhibitors tacrine and donepezil on A beta(25-35)-induced toxicity was investigated in rat pheochromocytoma PC12 cells by measuring the mitochondrial activity. Tacrine and donepezil was found in clinical relevant concentrations (10(-7)-10(-6) M) to attenuate A beta(25-35)-induced toxicity in PC12 cells. The neuroprotective effect of tacrine was blocked in the presence of the nicotinic antagonists mecamylamine (10(-5) M) and tubocurarine (10(-5) M), suggesting an interaction via nicotinic receptors. This study demonstrates that tacrine and donepezil can exert neuroprotective properties which might be of importance and contribute to the clinical efficacy of cholinesterase inhibitors in the treatment of Alzheimer's disease.
Svensson
A L
AL
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital B84, Sweden.
Nordberg
A
A
D000310:Adrenal Gland Neoplasms; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D008464:Mecamylamine / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D010673:Pheochromocytoma; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D013619:Tacrine / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D010880:Piperidines; C074636:amyloid beta-protein (25-35); D013619:Tacrine; D008464:Mecamylamine; D000077265:Donepezil; D014403:Tubocurarine