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Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity.
Eur J Pharmacol. 2006 Jan 20; 530(3):215-22.EJ

Abstract

Donepezil has a neuroprotective effect against oxygen-glucose deprivation injury and glutamate toxicity in cultured cortical neurons. In this study, we further characterized the neuroprotective properties of donepezil in rat cortical cell cultures using glutamate receptor-specific agonists (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate). Pretreatment with donepezil (1 microM) for 12 h significantly decreased the lactate dehydrogenase (LDH) release in response to NMDA (100 microM) by 43.8%, and reduced the LDH release in response to kainate (100 microM) and AMPA (100 microM) by 11.9% and 7.5% (without statistical significance), respectively. Donepezil appeared to inhibit LDH release in a concentration-dependent manner at 0.1-10 microM. Cortical neurons exposed to NMDA retained a normal morphological appearance in the presence of 10 microM donepezil. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. On the other hand, 12 h pretreatment with donepezil at 10 and 100 microM significantly decreased the NMDA-induced increase of intracellular calcium concentration ([Ca2+]i). In conclusion, our results show that donepezil has protective activity against NMDA toxicity in cortical neurons, and this neuroprotection seems to be partially mediated by inhibition of the increase of [Ca2+]i.

Authors+Show Affiliations

Tsukuba Research Laboratories, Eisai Co., Ltd. 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16406045

Citation

Akasofu, Shigeru, et al. "Protective Effect of Donepezil in Primary-cultured Rat Cortical Neurons Exposed to N-methyl-d-aspartate (NMDA) Toxicity." European Journal of Pharmacology, vol. 530, no. 3, 2006, pp. 215-22.
Akasofu S, Kimura M, Kosasa T, et al. Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity. Eur J Pharmacol. 2006;530(3):215-22.
Akasofu, S., Kimura, M., Kosasa, T., Ogura, H., & Sawada, K. (2006). Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity. European Journal of Pharmacology, 530(3), 215-22.
Akasofu S, et al. Protective Effect of Donepezil in Primary-cultured Rat Cortical Neurons Exposed to N-methyl-d-aspartate (NMDA) Toxicity. Eur J Pharmacol. 2006 Jan 20;530(3):215-22. PubMed PMID: 16406045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity. AU - Akasofu,Shigeru, AU - Kimura,Manami, AU - Kosasa,Takashi, AU - Ogura,Hiroo, AU - Sawada,Kohei, PY - 2005/11/23/received PY - 2005/11/28/accepted PY - 2006/1/13/pubmed PY - 2006/3/11/medline PY - 2006/1/13/entrez SP - 215 EP - 22 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 530 IS - 3 N2 - Donepezil has a neuroprotective effect against oxygen-glucose deprivation injury and glutamate toxicity in cultured cortical neurons. In this study, we further characterized the neuroprotective properties of donepezil in rat cortical cell cultures using glutamate receptor-specific agonists (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate). Pretreatment with donepezil (1 microM) for 12 h significantly decreased the lactate dehydrogenase (LDH) release in response to NMDA (100 microM) by 43.8%, and reduced the LDH release in response to kainate (100 microM) and AMPA (100 microM) by 11.9% and 7.5% (without statistical significance), respectively. Donepezil appeared to inhibit LDH release in a concentration-dependent manner at 0.1-10 microM. Cortical neurons exposed to NMDA retained a normal morphological appearance in the presence of 10 microM donepezil. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. On the other hand, 12 h pretreatment with donepezil at 10 and 100 microM significantly decreased the NMDA-induced increase of intracellular calcium concentration ([Ca2+]i). In conclusion, our results show that donepezil has protective activity against NMDA toxicity in cortical neurons, and this neuroprotection seems to be partially mediated by inhibition of the increase of [Ca2+]i. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16406045/Protective_effect_of_donepezil_in_primary_cultured_rat_cortical_neurons_exposed_to_N_methyl_d_aspartate__NMDA__toxicity_ DB - PRIME DP - Unbound Medicine ER -