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)

Abstract

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
JournalNeuropharmacology
Volume32
DOIs
Publication statusPublished - 1993

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