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 mu M 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. (C) 1998 Elsevier Science B.V. All rights reserved.