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Neuroprotective sigma ligands interfere with the glutamate-activated NOS pathway in hippocampal cell culture by Anne S. Lesage; Katrien L. De Loore; Luc Peeters; Josee E. Leysen is a Neuroscience article available to read on EtoBox.
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## Abstract We studied neuroprotective properties of 12 structurally different sigma site ligands in primary rat hippocampal cell cultures and analyzed whether they interfere with glutamate‐induced activation of the nitric oxide synthase (NOS) pathway. Neurotoxicity was triggered with 1mM glutamate on day 8 of culture. Cells were treated with various concentrations of the compounds for 7 days before glutamate exposure (prolonged pretreatment), or during glutamate exposure (acute treatment). Protection was seen after prolonged pretreatment (long‐term protection) with sabeluzole, opipramole, haloperidol, ifenprodil, fenpropimorph, carbetapentane, and tiospirone, with pIC~50~S of 7.30, 7.15, 6.87, 6.68, 6.66, 6.39, and 6.34, respectively. There was no protection with PD 128298, 1,3‐ortho‐di‐tolylguanidine, BMY‐14802, (+)3‐(3‐hydroxyphenyl)‐N‐l(propy1) piperidine, or dextromethorphan. Upon acute treatment, only ifenprodil was protective. Interference of the drugs with glutamate activation of the NOS pathway was determined by measuring glutamate‐activated cGMP formation and citrulline levels. Glutamate‐activated cGMP formation was reduced by all neuroprotective sigma ligands after prolo
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- Author
- Anne S. Lesage; Katrien L. De Loore; Luc Peeters; Josee E. Leysen
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0887-4476)
- Published
- 1995
- Language
- EN
- Field
- Neuroscience (Life Sciences)
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