Related Experiment Video
Updated: Aug 18, 2026
Optimization of Transesophageal Atrial Pacing to Assess Atrial Fibrillation Susceptibility in Mice
Published on: June 29, 2022
Amiodarone fails to improve survival in amitriptyline-poisoned mice
Fermin Barrueto1, Amy Chuang, Brian W Cotter
1Division of Emergency Medicine, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. fbarr001@umaryland.edu
Objective:
Amiodarone, a class III antidysrhythmic agent, blocks Na+, Ca2+, and K+ channels as well as the beta-adrenergic receptor. Despite increased use of amiodarone for wide-complex tachycardia, its efficacy in the treatment of dysrhythmias induced by tricyclic antidepressants has not been tested. We investigated the effect of amiodarone and amitriptyline in a mouse lethality model.
Methods:
The LD50 of amitriptyline obtained from reference sources was confirmed by giving 100 mg/kg to 40 mice by intraperitoneal (IP) injection. The safety of the treatment dose of amiodarone was confirmed by giving 50 mg/kg by IP injection to 10 mice. One hundred and nine mice were randomized to receive pretreatment with 50 mg/kg amiodarone (n=55) or an equal volume of saline or water as a volume control (n=54). Thirty minutes after pretreatment or control injection, the mice received amitriptyline, 100 mg/kg. Outcome was defined as death or survival 3 h after amitriptyline injection.
Results:
In our confirmation of the LD50 of amitriptyline, 25/40 mice died (62.5%). None of the 10 mice that received only amiodarone died. In the control + amitriptyline arm, 36/54 (66.7%) died, compared with 39/55 (70.9%) in the amiodarone+amitriptyline arm (X2, p=0.663). Power analysis demonstrated a 90% chance of finding a 28% difference.
Conclusions:
Pretreatment with amiodarone does not appear to significantly alter the lethality of amitriptyline poisoning in mice. Given the inability to monitor cardiac activity in this model, further investigation in a larger animal is required.
Insights
Amiodarone did not significantly change the lethality of amitriptyline poisoning in mice. Further studies in larger animals are needed to confirm these findings on antidysrhythmic drug efficacy.
Area of Science:
- Pharmacology
- Toxicology
- Cardiology
Background:
- Amiodarone is a class III antidysrhythmic agent affecting multiple ion channels.
- Tricyclic antidepressants can induce life-threatening dysrhythmias.
- The efficacy of amiodarone in treating tricyclic antidepressant-induced dysrhythmias is unknown.
Purpose of the Study:
- To investigate the effect of amiodarone on amitriptyline-induced lethality in a mouse model.
- To assess amiodarone's potential as a treatment for tricyclic antidepressant poisoning.
Main Methods:
- Mice were pretreated with amiodarone (50 mg/kg IP) or saline control.
- Amitriptyline (100 mg/kg IP) was administered 30 minutes post-pretreatment.
- Lethality was assessed 3 hours after amitriptyline administration.
Main Results:
- Amitriptyline LD50 was confirmed at 62.5% mortality.
- Amiodarone alone was not lethal at the tested dose.
- Mortality rates were similar between amiodarone-treated (70.9%) and control (66.7%) groups.
Conclusions:
- Amiodarone pretreatment did not significantly alter amitriptyline lethality in mice.
- The study suggests amiodarone is not effective in this specific model of tricyclic antidepressant poisoning.
- Further research in larger animal models is necessary due to limitations in monitoring cardiac activity.
Related Concept Videos
01:25Cardiopulmonary Resuscitation IV: Pharmacological Management
01:12Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
01:26Heart Failure Drugs: Inotropic Agents
01:19Depolarizing Blockers: Pharmocokinetics