Dapoxetine induces neuroprotective effects against glutamate-induced neuronal cell death by inhibiting calcium signaling and mitochondrial depolarization in cultured rat hippocampal neurons.

Dapoxetine induces neuroprotective effects against glutamate-induced neuronal cell death by inhibiting calcium signaling and mitochondrial depolarization in cultured rat hippocampal neurons. Eur J Pharmacol. 2017 Mar 16;: Authors: Jeong I, Seon Yang J, Jae Hong Y, Jung Kim H, June Hahn S, Hee Yoon S Abstract Selective serotonin reuptake inhibitors (SSRIs) have an inhibitory effect on various ion channels including Ca(2+) channels. We used fluorescent dye-based digital imaging, whole-cell patch clamping and cytotoxicity assays to examine whether dapoxetine, a novel rapid-acting SSRI, affect glutamate-induced calcium signaling, mitochondrial depolarization and neuronal cell death in cultured rat hippocampal neurons. Pretreatment with dapoxetine for 10min inhibited glutamate-induced intracellular free Ca(2+) concentration ([Ca(2+)]i) increases in a concentration-dependent manner (Half maximal inhibitory concentration= 4.79µM). Dapoxetine (5 μM) markedly inhibited glutamate-induced [Ca(2+)]i increases, whereas other SSRIs such as fluoxetine and citalopram only slightly inhibited them. Dapoxetine significantly inhibited the glutamate-induced [Ca(2+)]i responses following depletion of intracellular Ca(2+) stores by treatment with thapsigargin. Dapoxetine markedly inhibited the metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine-induced [Ca(2+)]i increases. Dapoxetine significantly inhibited the glutamate and α-amino-...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research