Protective effects of clonidine and verapamil in experimental amitriptyline poisoning in rabbits

The effects of various agents on acute amitriptyline-induced cardiotoxicity were investigated in conscious rabbits. Amitriptyline (50 mg/kg, IP) regularly produced consistent and reproducible electrocardiographic changes such as lengthening of Q-T intervals, widening of the QRS complex, arrhythmias of various types, convulsion, and severe hypotension. Prevention of these toxic manifestations by the use of various agents alone or in combination was explored. Clonidine (50 micrograms/kg, IV) and verapamil (0.25 mg/kg, IV) alone or in combination at lower doses (25 micrograms/kg plus 0.125 mg/kg, respectively) significantly reduced the lengthening of the QRS and Q-T intervals, restored sinus rhythm, maintained blood pressure at a constant level, and protected against a lethal dose of amitriptyline (75 mg/kg). These results suggest that verapamil, clonidine, and their combination appear to be promising antidotal agents in restoring cardiac function under these conditions.