SB 201823-A, A neuronal Ca antagonist is neuroprotective in two models of cerebral ischaemia

C.D. Benham, T.H. Brown, D.C. Cooper, M.L. Evans, M. Harries, H.J. Herdon, J.E. Meakin, K.L. Murkitt, S. Patel, J.C. Roberts, A.L. Rothaul, S.J. Smith, N. Wood, A.J. Hunter

    Research output: Contribution to journalArticlepeer-review

    43 Citations (Scopus)


    We have characterised the Ca2+ channel blocking properties of a new non-peptide Ca2+ channel antagonist, SB 201823-A, in cultures of rat sensory neurones. The IC50 for SB 201823-A against total Ca2+ current in sensory neurones was 4.9 μM. SB 201823-A showed little selectivity for sub-types of neuronal Ca2+ channel but was selective for Ca2+ channels over Na+ and K+ channels. Efficacy against other types of cation channel 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 photothrombotic focal lesion model, SB 201823-A administered i.p. 10 min post-ischaemia resulted in a dramatic reduction in lesion volume. In the gerbil bilateral carotid artery occlusion global model, SB 201823-A dosed i.p. 30 min post-occlusion resulted in both histological and functional improvements when compared to vehicle treated animals. These data suggest that such novel neuronal Ca2+ channel antagonists may have potential in ameliorating both the pathological and functional consequences of stroke in man.

    Original languageEnglish
    Pages (from-to)1249-1257
    Publication statusPublished - 1993


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