Abstract
The action of phenylalkylamine Ca 2+ channel blockers D890 and D888 on Ca 2+ uptake and neurotransmitter amino acid release were studied. D890, the quaternary derivative of D600, did not inhibit veratrine-induced 45Ca 2+ uptake or the release of neurotransmitter amino acids from rat cerebrocortical synaptosomes, except at high concentrations (200 μM) when it was probably acting extracellularly in a non-specific manner. This contrasted with the more potent (10–50 μM) inhibitory actions of D600 and D888, and may be due to the inability of D890 to cross the synaptic plasma membrane. (−)D888 was shown to cross cell membranes and accumulate in the intracellular compartment of cerebrocortical slices and synaptosomes, where it was associated predominantly with the soluble cytoplasmic fraction.
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