A Preclinical Study of EO-122, a New Lidocine-Like Antiarrhythmic Drug

Oppenheimer, Edna; Kaplinsky, Eliezer; Kariv, Naam; Bruckstein, Rachel; Cohen, Sasson
June 1980
Angiology;Jun1980, Vol. 31 Issue 6, p410
Academic Journal
The 2,6-dimethylanilide of quinuclidine-3-carboxyUc acid hydrochloride (EO-122), a new structural analog of lidocaine, has been shown to possess potent antiarrhythmic activity in experimentally induced arrhythmias in animals. Restoration of normal sinus rhythm and suppression of ouabain-induced arrhythmia in cats and dogs, and of coronary occlusion-induced arrhythmia in dogs, followed a single IV injection of 1-3 mg/kg, with an onset of 2 minutes and a duration of 20-240 minutes. Occlusion-induced arrhythmia was likewise suppressed after an oral dose of 10-20 mg/kg, with an onset of 11-65 minutes and a duration of 25-120 minutes. Under similar conditions, lidocaine was either totally ineffective or of ultra-short duration. The bioavailability of EO-122 by the oral route exceeded 80% of the oral dose. Therapeutic blood concentrations were in the range 0.5-7 μg/ml. At about 5/μg/ml there was a slight depression of cardiac function in the anesthetized cat, but not in the conscious dog. In cats, complete A-V block occurred at concentrations of 60-70 μg/ml. The IV LD50 in mice was 22 mg/kg, and in rabbits 8.5 mg/kg. No overt signs of neurotoxicity could be observed at any dose of EO-122. The pharmacokinetic profile of the drug fits a two-compartment open model, with t⅛ ≃ 150 min and Vd (ss) ≃ 1.5 1/kg.


Related Articles

  • Min-I-Jet Lignocaine.  // Royal Society of Medicine: Medicines;2002, p366 

    This article focuses on Min-I-Jet Lignocaine, a proprietary, prescription-only preparation of the local anaesthetic lidocaine hydrochloride that can be used as an anti-arrhythmic drug to treat irregularities in the heartbeat, especially after a heart attack and is available in a form for injection.

  • Intravenous Antiarrhythmic Drugs: Newer Aspects of Therapy. Abbott, Joseph A. // Angiology;Apr1982, Vol. 33 Issue 4, p251 

    Discusses aspects of therapy for tachyarrhythmias. Clinical relevance of experimental antiarrhythmic drugs that may be infused intravenously; Purposes of using intravenous antiarrhythmic drugs; Prevention of potentially fatal arrhythmia.

  • Lidocaine may block an ATP-dependent K+ channel. Dale, David C.; Federman, Daniel D. // Cortlandt Forum;12/20/97, Vol. 10 Issue 12, p20 

    Reports that class IB antiarrhythmic drugs are less powerful sodium ion (Na+) channel blockers than class IA drugs. Reason why class IB agents are less powerful.

  • Update on Atrial Fibrillation: Restoration of Sinus Rhythm or Ventricular Rate Control? Yi-Gang Li; Hohnloser, Stefan H. // Journal of Cardiovascular Pharmacology & Therapeutics;Jun1998, Vol. 3 Issue 2, p185 

    The article discusses therapeutic alternatives for patients with persistent atrial fibrillation. It summarizes the present knowledge on this clinical problem with particular emphasis on issues such as efficacy of antiarrhythmic drugs to prevent recurrent atrial fibrillation, proarrhythmic...

  • Antiarrhythmic Drug Therapy for Atrial Fibrillation: Focus on Atrial Selectivity and Safety. Li, D.; Sun, H.; Levesque, P. // Cardiovascular & Hematological Agents in Medicinal Chemistry;2009, Vol. 7 Issue 1, p64 

    Atrial fibrillation (AF) is a highly prevalent arrhythmia and responsible for significant morbidity, mortality and health care cost. The prevalence of AF is expected to increase markedly with the aging population. The use of conventional antiarrhythmic agents has been limited by potentially...

  • Assessment of the Inactivation Potential of Desethylamiodarone on Human CYP1A1. Elsherbiny, Marwa E.; El-Kadi, Ayman O. S.; Brocks, Dion R. // Drug Metabolism Letters;Jan2010, Vol. 4 Issue 1, p9 

    Desethylamiodarone was reported to inactivate human CYP1A1. To assess this, two protocols were implemented employing dilution and non-dilution of the preincubation mixture. Inactivation studies performed with diluted preincubation mixtures showed no inactivation of CYP1A1 by desethylamiodarone....

  • Rythmodan Retard.  // Royal Society of Medicine: Medicines;2002, p483 

    The article presents information on rhythmodan retard, a proprietary, prescription-only preparation of the anti-arrhythmic disopyramide. It is available as modified-release tablets.

  • Atrial Fibrillation: The Rate or Rhythm Controversy. Singh, Bramah N. // Journal of Cardiovascular Pharmacology & Therapeutics;Jun2005, Vol. 10 Issue 2, p81 

    Explores studies on rhythm controversy in atrial fibrillation. Direction of an increase in mortality in the subset of patients randomized to sinus rhythm; Results of a placebo-controlled trial of restoration and maintenance of sinus rhythm; Properties of sotalol and amiodarone as atrial...

  • tocainide.  // Davis's Drug Guide for Nurses, 10th edition;2007, p1157 

    This article presents a nurse's guide to the antiarrhytmic agent tocainide. Tocainide is indicated for the treatment of life-threatening ventricular arrhythmias, including multifocal and unifocal premature ventricular contractions and ventricular tachycardia. Tocainide works by suppressing...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics