Antagonist drug selectivity for radioligand binding sites on voltage-gated and N-methyl-D-aspartate receptor-gated Ca2+ channels.

Drugs that block voltage-gated Ca2+ channels or N-methyl-D-aspartate receptor-gated channels have been shown to reduce experimental hypoxic-ischemic neuronal injury. To determine if any such compounds interact with both types of channels, and might therefore be prototypes for new anti-ischemic drugs with dual therapeutic actions, we compared the affinities of channel blockers for voltage-gated Ca2+ channel binding sites labeled by (+)-[3H]PN 200-110 and N-methyl-D-aspartate receptor-gated channel sites labeled by [3H]MK-801. Combined effects were most prominent with dextromethorphan, followed by D-888, verapamil and dextrorphan.