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배양한 대뇌피질세포에서 유발한 신경손상에 대한 콜린에스테라제 억제제의 영향
독고향(Hyang Dok Go),이광헌(Kwang Heun Lee),조정숙(Jung Sook Cho) 대한약학회 2002 약학회지 Vol.46 No.3
Alzheimer's disease (AD) involves neuronal degeneration with impaired cholinergic transmission, particularly in areas of the brain associated with learning and memory: Several cholinesterase inhibitors are widely prescribed to ameliorate the cognitive deficits in AD patients. In an attempt to examine if tacrine and donepezil, two well- known cholinesterase inhibitors, exhibit additional pharmacological actions in primary cultured rat cortical cells, we investigated the effects on neuronal injuries induced by glutamate or N-methyl-D-aspartate (NMDh), β-amyloid fragment (Aβ(25- 35)), and vatslous oxidative insults. Both tacrine and donepezil did not significantly inhibit the excitotoxic neuronal damage induced by g1utamate. However, taurine inhibited the toxicity induced by NMDh in a concentration-dependent fashion. In addition, taurine significantly inhibited the Aβ(25-35)-induced neuronal injury at the concentration of 50μM. In contrast, donepezil did not reduce the NMDA- nor Aβ(25-35))-induced neuronal injury, Tacrine and donepezil had no effects on oxidative neuronal injuries in cultures nor on lipid peroxidation in vitro. These results suggest that, in addition to its anticholinesterase activity the neuroprotective effects by taurine against the NMDA- and Aβ(25-35)-induced toxicity may be beneficial for the treatment of hn. In contrast, the potent and selective inhibition of central acetylcholinesterase appears to be the major action mechanism of donepezil.
ScienceON
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