THE 5-HT1A RECEPTOR AGONIST BAY-X-3702 PREVENTS STAUROSPORINE-INDUCEDAPOPTOSIS

The 5-HT1A receptor agonist ino]butyl]-1,2-benzisothiazol-3(2H)-one1,1 -dioxide monohydrochloride (BAY x 3702) was recently shown to have pro nounced neuroprotective effects in rat models of cerebral ischemia and traumatic brain injury. In the present study we investigated the neur oprotective effects of BAY x 3702 in primary cultures of hippocampal a nd cortical neurons. Cell death was induced by 25 nM of the apoptosis inducing agent staurosporine and analyzed 24 h later by release of lac tate dehydrogenase, formation of apoptotic bodies and DNA fragmentatio n. A significant neuroprotection was seen after pretreatment of the af fected neurons with 50 pM to 1 mu M BAY x 3702. The effects of BAY x 3 702 were completely blocked by the selective 5-HT1A receptor antagonis t ethoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexanecarbox amide trihydrochloride) (WAY-100635). These results indicate that low concentrations of BAY x 3702 protect cortical as well as hippocampal n eurons from apoptotic cell death via a 5-HT1A receptor mediated pathwa y. (C) 1998 Elsevier Science B.V. All rights reserved.