Experimental studies on the effects of physostigmine and of isoproterenol on toxicity produced by tricyclic antidepressant agents.

The IV infusion of nortriptyline and amitriptyline (0.5 mg/kg/min) in anesthetized cats produced death within 60 min of continuous infusion. The tricyclic antidepressant agents produced a quinidine-like depression of the myocardium characterized by bradycardia, depression of contractile force, conduction defects, bradyarrhythmias, and hypotension. The simultaneous IV infusion of isoproterenol (0.1 microgram/ kg/min) produced significant protection against death produced by the TCA drugs. The results suggested that the positive chronotropic, inotropic, and dromotropic actions of isoproterenol may all be contributory factors in the protection. Pretreatment with a large dose of physostigmine (0.2 mg/kg) produced a rightward shift of the nortriptyline time-mortality curve. The small degree of protection produced by the anticholinesterase drug may be due to a respiratory stimulant action rather than a cardiac action.