Effect of TTC-909, an isocarbacyclin methyl ester (clinprost) incorporatedinto lipid microspheres, on neuronal damage induced by cerebral ischemia.

TTC-909 is a drug preparation of clinprost. This novel prostacyclin analogu e was incorporated into lipid microspheres. Clinprost is released gradually from lipid microspheres, and is hydrolyzed to TEI-7165 by esterase action to exert pharmacological activity. TTC-909, given 10 min after transient is chemia (10 min 2 vessels occlusion model), dose-dependently protected again st delayed neuronal death of the hippocampal CA1 neurons in SHRSP. TEI-7165 , infused into the lateral ventricle of gerbils for 7 days starting 2 hours before induced 3-min forebrain ischemia, using an osmotic mini-pump, prote cted against neuronal damage in the hippocampal CA1 region and against redu ction of synapses within the strata moleculare, radiatum and oriens of the region. In rat striatal slices, TEI-7165 and clinprost inhibited the elevat ion of intracellular Ca2+ levels ([Ca2+](i)) induced by BAY K 8644, determi ned using the fura-2 method. Furthermore, TEI-7165 and clinprost protected against BAY K 8644-induced striatal dysfunction, under conditions of transi ent ischemia. These results suggest that TTC-909 has a neuroprotective effe ct as a result of a direct action of TEI-7165 in cases of cerebral ischemia , possibly by inhibiting the elevation of [Ca2+](i).