B. Suchanek et al., THE 5-HT1A RECEPTOR AGONIST BAY-X-3702 PREVENTS STAUROSPORINE-INDUCEDAPOPTOSIS, European journal of pharmacology, 355(1), 1998, pp. 95-101
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.