title: Amiodarone fails to improve survival in amitriptyline-poisoned mice.
abstract: 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.
authors.affiliation: Division of Emergency Medicine, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. fbarr001@umaryland.edu
authors.forename: Fermin
authors.initials: F
authors.lastname: Barrueto
authors.forename: Amy
authors.initials: A
authors.lastname: Chuang
authors.forename: Brian W
authors.initials: BW
authors.lastname: Cotter
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoffman
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Nelson
mesh_terms: D000638:Amiodarone / Q000627:therapeutic use*; D000639:Amitriptyline / Q000506:poisoning*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000506:poisoning*; D004195:Disease Models, Animal; D005260:Female; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D011041:Poisoning / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
chemical_list: D000889:Anti-Arrhythmia Agents; D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D000638:Amiodarone