SB-201823-A, A NEURONAL CA2-ISCHEMIA( ANTAGONIST IS NEUROPROTECTIVE IN 2 MODELS OF CEREBRAL)

We have characterised the Ca2+ channel blocking properties of a new no n-peptide Ca2+ channel antagonist, SB 201823-A, in cultures of rat sen sory neurones. The IC50 for SB 201823-A against total Ca2+ current in sensory neurones was 4.9 muM. SB 201823-A showed little selectivity fo r sub-types of neuronal Ca2+ channel but was selective for Ca2+ channe ls over Na+ and K+ channels. Efficacy against other types of cation ch annel such as agonist gated channels was not assessed. SB 201823-A was neuroprotective in vivo when administered post-ischaemia in one focal and one global model of neuronal ischaemia. In the rat photothromboti c focal lesion model, SB 201823-A administered i.p. 10 min post-ischae mia resulted in a dramatic reduction in lesion volume. In the gerbil b ilateral carotid artery occlusion global model, SB 201823-A dosed i.p. 30 min post-occlusion resulted in both histological and functional im provements when compared to vehicle treated animals. These data sugges t that such novel neuronal Ca2+ channel antagonists may have potential in ameliorating both the pathological and functional consequences of stroke in man.