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Local anesthetic activity and disopyramide toxicity.

In the isolated frog sciatic nerve preparation, IC50 concentrations for nerve block were 0.34 +/- 0.9 mM for lidocaine (LIDO), 0.62 +/- 0.11 mM for procaine, 11.9 +/- 6.1 mM for disopyramide (DIP), and 52.8 +/- 24 mM for MIP (the mono-demethylated metabolite of DIP). In contrast to the LIDO block, DIP-induced nerve block was irreversible. DIP-induced depression of the electrically stimulated rat ventricular strip was completely reversed by washing the drug-free Tyrode's solution. In mice receiving 250 mg/kg DIP, neither convulsions nor death could be prevented by diazepam or other anticonvulsants. These results suggest that DIP has a very weak local anesthetic action which does not contribute significantly to disopyramide toxicity.