PT  - JOURNAL ARTICLE
AU  - C H Follmer
AU  - B K Lum
TI  - Protective action of diazepam and of sympathomimetic amines against amitryptyline-induced toxicity.
DP  - 1982 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 424--429
VI  - 222
IP  - 2
4099  - http://jpet.aspetjournals.org/content/222/2/424.short
4100  - http://jpet.aspetjournals.org/content/222/2/424.full
SO  - J Pharmacol Exp Ther1982 Aug 01; 222
AB  - Factors that contribute to the lethality of amitriptyline overdosage were studied in cats. Amitriptyline (50 mg/kg) given i.p. to unanesthetized cats produced convulsions in all of the animals and death in five of six animals; pretreatment with diazepam (5 mg/kg) protected against the convulsions and death. Respiratory depression contributed to the mortality when amitriptyline was given i.v. in cats anesthetized with pentobarbital as indicated by the finding that artificial respiration delayed the time of death induced by a continuous i.v. infusion of the drug. The i.v. infusion of amitriptyline in pentobarbitalized cats under artificial respiration produced death due to cardiovascular collapse. The latter was characterized by hypotension, bradycardia, depression of myocardial contractile force, atrioventricular block, intraventricular conduction delay and cardiac arrhythmias. These effects appear to be due to a direct membrane (quindine-like) cardiotoxic action of amitriptyline. Dopamine and dobutamine were effective in protecting the animals against the acute cardiovascular collapse induced by amitriptyline. The protection was associated with a diminution of the hypotension, the negative inotropic and chronotropic actions and the incidence of atrioventricular block produced by the tricyclic antidepressant drug. The results suggest that the positive chronotropic, inotropic and dromotropic actions of the amines may all be contributory factors in their protection action. Isoproterenol and norepinephrine were less effective than the other two amines.