Amiodarone Fails to Improve Survival in Amitriptyline-Poisoned Mice

Barrueto, Fermin; Chuang, Amy; Cotter, Brian; Hoffman, Robert M.; Nelson, Lewis S.

doi:10.1081/clt-200053076

Cited by 4 publications

(5 citation statements)

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“…et al found that an i.p. LD 50 dose of amitriptyline was 100 mg/ kg in female Swiss Albino mice (Barrueto et al, 2005). This difference at LD 50 doses of amitriptyline may be explained by the differences in sex and species.…”

Section: Discussionmentioning

confidence: 85%

“…Three different doses of amitriptyline (125, 100, and 75 mg/kg) were given to 60 mice (n = 20 for each dose, finally n = 60) by i.p. injection (Barrueto et al, 2005). Similarly, the nonlethal dose of selective adenosine A 1 -and A 2areceptor antagonists (i.e., DPCPX and CSC) was confirmed (1, 3, and 5 mg/kg; n = 10 for each dose, n = 30 for each antagonist, finally for two antagonists n = 60) by i.p injection (Prediger and Takahashi, 2005;Bové et al, 2002).…”

Section: Preliminary Studymentioning

confidence: 99%

See 1 more Smart Citation

Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

Kalkan

Hocaoğlu

Arıcı

et al. 2010

Drug and Chemical Toxicology

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Section: Discussionmentioning

confidence: 85%

Section: Preliminary Studymentioning

confidence: 99%

Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

Kalkan

Hocaoğlu

Arıcı

et al. 2010

Drug and Chemical Toxicology

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“…23 The LD50 value for IP administered amitriptyline was used as described in the literature. 21,24 We preferred to deliver the drug IP, based on the fact that this route of administration (IP injection) requires minimal skill and does not result in lesions or signs of pain when drugs are administered. Also, IP injection has the advantage of being both simple and also causes minimum distress to the rats.…”

Section: Discussionmentioning

confidence: 99%

“…Different groups of rats were injected intraperitoneally (IP) with one of the following formulations: (1) amitriptyline-Arena Group S.A., Bucharest, Romania, (n ¼ 18), 100 mg/kg body weight (equivalent for IP lethal dose at 50% [LD50]) 21 in 1 mL NaCl 9% saline vehicle and (2) 1 mL saline for the control group (n ¼ 6).…”

Section: Drugs Administration and Sample Collectionmentioning

confidence: 99%

Cardiac Troponin T and NT-proBNP as Biomarkers of Early Myocardial Damage in Amitriptyline-Induced Cardiovascular Toxicity in Rats

et al. 2013

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The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P< .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.

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“…An initial mouse survival study showed that there was no statistical difference in the amitriptyline LD 50 of mice pretreated with amiodarone when compared to a normal saline control [6]. Since hemodynamic monitoring and electrocardiographic (ECG) analysis were not possible in that small-animal model, a swine model was devised to evaluate these critical measures.…”

Section: Effects Of Amiodarone In a Swine Model Of Nortryptiline Toximentioning

confidence: 99%

Effects of amiodarone in a swine model of nortryptiline toxicity

et al. 2006

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Objectives: Antiarrhythmics can have devastating effects in cardiotoxic poisonings. Amiodarone is recommended for treatment of wide complex tachycardia, but its hemodynamic effects in wide complex tachycardia induced by tricyclic antidepressant poisoning are unknown. The objective of this study was to compare the effects of sodium bicarbonate, amiodarone, and normal saline in treating wide complex tachycardia secondary to nortriptyline poisoning.Methods: This unblended randomized controlled animal study involved 18 anesthetized, intubated pigs with arterial and venous lines. Nortriptyline (2 mg/mL) was infused at 20 mg/min until the onset of toxicity, defined as a systolic blood pressure ≤50 mmHg or QRS ≥120 ms. At that point, the pigs were randomized into three groups of six. Group I received 0.9% normal saline, 10 ml/kg. Group II received hypertonic sodium bicarbonate, 1 mEq/kg. Group III received amiodarone, 15 mg/kg. The pigs were observed until death or survival at 60 minutes.Results: After treatment, the changes in QRS were as follows: Group I, −2.0 ms; Group II, −33.0 ms; Group III, −21.7 ms. ANOVA demonstrated no significant difference between the groups (p = 0.28). Mean arterial pressures 10 minutes after treatment were as follows: Group I, 19.4 mmHg; Group II, 23.7 mmHg; Group III, 12.5 mmHg. Based on ANOVA, there was no significant difference between any of the groups (p = 0.50).Conclusions: In this model of nortriptyline poisoning, the administration of amiodarone to correct wide complex tachycardia did not have a harmful effect.

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Amiodarone Fails to Improve Survival in Amitriptyline-Poisoned Mice

Abstract: 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.

Cited by 4 publications

References 5 publications

Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

Cardiac Troponin T and NT-proBNP as Biomarkers of Early Myocardial Damage in Amitriptyline-Induced Cardiovascular Toxicity in Rats

Effects of amiodarone in a swine model of nortryptiline toxicity

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