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 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.
Suchanek
B
B
Bayer, CNS Research, Pharma-Forschungszentrum, Wuppertal, Germany. bettina.suchanek.bs@bayer-ag.de
Struppeck
H
H
Fahrig
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D053938:DNA Fragmentation; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D019311:Staurosporine; D013844:Thiazoles / Q000494:pharmacology*
D001578:Benzopyrans; D018696:Neuroprotective Agents; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; C111221:repinotan hydrochloride; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D019311:Staurosporine