EO-199, a specific antagonist of antiarrhythmic drugs: assessment by binding experiments and in vivo studies.
EO-199, a demethylated analog of the novel class I antiarrhythmic drug EO-122 was found to antagonize the antiarrhythmic activity of EO-122 and that of procainamide (Class IA). EO-199 did not block significantly the activity of a class IB antiarrhythmic agent, lidocaine. EO-199 also displaced the specific binding of [3H]EO-122 to rat heart membranes similarly to procainamide whereas lidocaine did not. The correlation between binding experiments and pharmacological effects points to a possible subclassification of these drugs; the two chemical analogs EO-199 and EO-122, as well as procainamide (IA) but not lidocaine (IB), compete at the same site or the same state of the sodium channel. The availability of a specific antagonist might be useful for studying the mechanism of action of antiarrhythmic drugs as well as an antidote in cases of antiarrhythmics overdose intoxication.
Oppenheimer
E
E
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
Harel
G
G
Lipinsky
D
D
Sarne
Y
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D011342:Procainamide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011812:Quinuclidines / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D000889:Anti-Arrhythmia Agents; D011812:Quinuclidines; C067616:2'-methyl-3-quinuclidinylanilide; C026586:EO 122; D008012:Lidocaine; D011342:Procainamide