Neuroprotective effect of donepezil, a nicotinic acetylcholine-receptor activator, on cerebral infarction in rats.
This study evaluated the potential effect of donepezil, which is known as an acetylcholinesterase inhibitor used for treatment of Alzheimer's disease, against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion. Donepezil was given orally in various regimens, prior to MCA occlusion in rats. Pretreatment with a single oral dose of donepezil (12 mg/kg), 2 h before ischemia, significantly attenuated cerebral infarction volume (165.5 +/- 105.3 vs. 377.1 +/- 48.5 mm(3); P < 0.05). These neuroprotective effects were prevented by coinjection with mecamylamine, a nicotinic acetylcholine-receptor (nAChR) antagonist, indicating that protection was mediated by nAChR activation.
Fujiki
Minoru
M
Department of Neurosurgery, School of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan. fujiki@med.oita-u.ac.jp
Kobayashi
Hidenori
H
Uchida
Susumu
S
Inoue
Ryo
R
Ishii
Keisuke
K
D000818:Animals; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D019194:Ischemic Preconditioning; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology
D007189:Indans; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D010880:Piperidines; D011978:Receptors, Nicotinic; D000077265:Donepezil