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Neuroprotective compounds inhibit depolarisation‐evoked calcium transients in granule cells
Author(s) -
Hubert JeanPierre,
Doble Adam
Publication year - 1998
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199810)45:2<74::aid-ddr4>3.0.co;2-h
Subject(s) - veratridine , chemistry , pharmacology , calcium , neuroprotection , lamotrigine , nmda receptor , depolarization , anticonvulsant , glutamate receptor , biophysics , neuroscience , sodium channel , biochemistry , sodium , medicine , epilepsy , biology , receptor , organic chemistry
The effects of several neuroprotective or anticonvulsant compounds on depolarisation‐evoked calcium mobilisation in cultured rat cerebellar granule cells were compared using a calcium imaging method. Calcium transients were evoked by brief stimulations with N ‐methyl‐ D ‐aspartate (NMDA), veratridine, or potassium chloride. The compounds tested were aptiganel, felbamate, gabapentin, lamotrigine, lubeluzole, riluzole, RP 66055A, sipatrigine, and SR 57746A. Aptiganel and riluzole inhibited calcium transients evoked both by NMDA and by veratridine. On the other hand, none of the other potential neuroprotective compounds studied shared this dual mechanism of action. Lamotrigine, lubeluzole, RP 66055A, sipatrigine, and SR 57746A only blocked responses to veratridine, whereas felbamate only (and partially) inhibited responses mediated by means of the NMDA receptor. SR 57746A also blocked responses to potassium chloride, suggesting that this compound may act at the level of the voltage‐dependent calcium channel. Aptiganel, lubeluzole, and RP 66055 also blocked responses to potassium chloride, but only at concentrations considerably higher than those needed to block responses to veratridine. Gabapentin was unable to inhibit calcium transients evoked by any of the three depolarising agents. The effects of these various compounds on intracellular calcium homeostasis described here may be relevant to their therapeutic efficacy in the treatment of epilepsy and neurodegenerative disorders. Drug Dev. Res. 45:74–82, 1998. © 1998 Wiley‐Liss, Inc.