title: Amlodipine besylate and amlodipine camsylate prevent cortical neuronal cell death induced by oxidative stress.
abstract: We examined the neuroprotective effects of the long-acting third-generation dihydropyridine Ca(2+) antagonists, amlodipine besylate (AB) and amlodipine camsylate (AC), on neuronal cell death induced by oxidative stress. Cell viability and levels of free radicals and intracellular signaling proteins were measured after treating primary cultures of cortical neurons with AB, AC, and/or hydrogen peroxide (H(2) O(2) ) under various conditions. Cell viability was not affected by concentrations of AB or AC up to 5 μM but decreased at higher concentrations. Following H(2) O(2) exposure, the viability of cortical neurons decreased in a concentration-dependent manner; however, treatment with AB or AC up to 5 μM restored the viability of H(2) O(2) -injured cortical neurons. Treatment with H(2) O(2) increased the level of free radicals in cortical neurons, and pre-treatment with AB or AC counteracted this in a dose-dependent manner. Similarly, treatment with AB or AC reduced the declines in p85aPI3K, phosphorylated Akt, phosphorylated GSK-3β, heat-shock transcription factor-1, and Bcl-2 induced by H(2) O(2) , as well as the increases in cyclooxygenase-2, cytosolic cytochrome c, cleaved caspase 9, and cleaved caspase 3. Our results indicate that AB and AC exert similar neuroprotective effects by reducing oxidative stress, enhancing survival signals, and inhibiting death signals.
authors: Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.
authors: Young Joo
authors: YJ
authors: Lee
authors: Hyun-Hee
authors: HH
authors: Park
authors: Seong-Ho
authors: SH
authors: Koh
authors: Na-Young
authors: NY
authors: Choi
authors: Kyu-Yong
authors: KY
authors: Lee
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007211:Indoles; D018696:Neuroprotective Agents; D017311:Amlodipine; C007293:DAPI; D006861:Hydrogen Peroxide