HALOPERIDOL BLOCKS VOLTAGE-ACTIVATED CA2+ CHANNELS IN HIPPOCAMPAL-NEURONS

The Ca2+ channel antagonist action of the antipsychotic haloperidol was investigated using two functional assays of Ca2+ channel activity. Haloperidol dose dependently attenuated the rise in intracellular free Ca2+ ([Ca2+](i)) evoked by 50 mM extracellular K+ in Fura-2 loaded cultured rat hippocampal neurones with an IC50 (+/- S.E.M.) of 7.8 +/- 0.5 mu M and similarly reduced whole-cell Ba2+ currents (I-Ba) in voltage-clamped mouse hippocampal neurones with an IC50 value of 15.6 +/- 1.1 mu M. Block of whole-cell I-Ba by haloperidol was rapid, fully reversible, and was greater at more depolarized membrane potentials. Our data indicate that haloperidol non-selectively blocks neuronal voltage-gated Ca2+ channels at micromolar concentrations.