The 5-HT1A receptor agonist BAY x 3702 prevents staurosporine-induced apoptosis

The 5-HT1A receptor agonist (-)-(R)-2-[4-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]butyl]-1,2 -benzisothiazol-3(2H)-one1,1-dioxide monohydrochloride (BAY x 3702) was recently shown to have pronounced neuroprotective effects in rat models of cerebral ischemia and traumatic brain injury. In the...

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Bibliographic Details
Published in:European journal of pharmacology 1998-08, Vol.355 (1), p.95-101
Main Authors: SUCHANEK, B, STRUPPECK, H, FAHRIG, T
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Benzopyrans - pharmacology
Biological and medical sciences
Cells, Cultured
Cerebral Cortex - drug effects
DNA Fragmentation
Female
Hippocampus - drug effects
Medical sciences
Neurons - drug effects
Neuropharmacology
Neuroprotective agent
Neuroprotective Agents - pharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Piperazines - pharmacology
Pyridines - pharmacology
Rats
Receptors, Serotonin - drug effects
Receptors, Serotonin - metabolism
Receptors, Serotonin, 5-HT1
Serotonin Antagonists - pharmacology
Serotonin Receptor Agonists - pharmacology
Serotoninergic system
Staurosporine
Thiazoles - pharmacology
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Summary:The 5-HT1A receptor agonist (-)-(R)-2-[4-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]butyl]-1,2 -benzisothiazol-3(2H)-one1,1-dioxide monohydrochloride (BAY x 3702) was recently shown to have pronounced neuroprotective effects in rat models of cerebral ischemia and traumatic brain injury. In the present study we investigated the neuroprotective effects of BAY x 3702 in primary cultures of hippocampal and cortical neurons. Cell death was induced by 25 nM of the apoptosis inducing agent staurosporine and analyzed 24 h later by release of lactate dehydrogenase, formation of apoptotic bodies and DNA fragmentation. A significant neuroprotection was seen after pretreatment of the affected neurons with 50 pM to 1 microM BAY x 3702. The effects of BAY x 3702 were completely blocked by the selective 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (WAY-100635). These results indicate that low concentrations of BAY x 3702 protect cortical as well as hippocampal neurons from apoptotic cell death via a 5-HT1A receptor mediated pathway.
ISSN:0014-2999
1879-0712
DOI:10.1016/s0014-2999(98)00469-5