Interactions of local anesthetics with neuronal 1,4-dihydropyridine binding sites

A series of local anesthetics competed with 1,4-dihydropyridine [³H]PN 200 110 binding to synaptosomes from guinea pig cerebral cortex synaptosomes. Dibucaine (10^-3M) increased the dissociation rate of bound [³H]PN 200 110 consistent with an indirect, rather than competitive, interaction between local anesthetics and the 1,4-dihydropyridine site. The binding activities were compared to those previously available for local anesthetic competition with [³H]batrachotoxinin benzoate binding at a Na⁺ channel site. A linear correlation was observed between the two sets of activities with significantly higher activities being exhibited at the Na⁺ channel site. This relationship is consistent with the significant structural homologies exhibited between Na⁺ and Ca²⁺ channels.