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.
Jaffe
D B
DB
Department of Neurology, University of California, San Francisco 94110.
Marks
S S
SS
Greenberg
D A
DA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D017275:Isradipine; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010069:Oxadiazoles; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D017275:Isradipine