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.
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local; D000818:Animals; D004206:Disopyramide / Q000494:pharmacology / Q000633:toxicity*; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D011725:Pyridines / Q000633:toxicity*; D011894:Rana pipiens; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D013997:Time Factors
D000779:Anesthetics, Local; D011725:Pyridines; D004206:Disopyramide