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SB 201823-A, a neuronal Ca2+antagonist is neuroprotective in two models of cerebral ischaemia

Authors
Journal
Neuropharmacology
0028-3908
Publisher
Elsevier
Publication Date
Volume
32
Issue
11
Identifiers
DOI: 10.1016/0028-3908(93)90019-y
Keywords
  • Stroke
  • Calcium Channels
  • Ischaemia Models
Disciplines
  • Biology
  • Medicine

Abstract

Abstract We have characterised the Ca 2+ channel blocking properties of a new non-peptide Ca 2+ channel antagonist, SB 201823-A, in cultures of rat sensory neurones. The IC 50 for SB 201823-A against total Ca 2+ current in sensory neurones was 4.9 μM. SB 201823-A showed little selectivity for sub-types of neuronal Ca 2+ channel but was selective for Ca 2+ 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 Ca 2+ channel antagonists may have potential in ameliorating both the pathological and functional consequences of stroke in man.

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