Immediate Effects of Physostigmine on Amitriptyline-Induced QRS Prolongation

Abstract

Prior studies have suggested that physostigmine may be useful in reversing QRS prolongation due to amitriptyline toxicity. To investigate this question, we devised a pharmacologic model in rabbits utilizing an initial intravenous bolus of amitriptyline (4–6 mg) followed by a constant amitriptyline infusion (0.2–0.4 mg/min) empirically titered to maintain the QRS at 50% or more of control value for at least 5 min. Intravenous physostigmine (2 mg) sufficient to produce muscle fasciculations and significant (P < 0.01) slowing of sinus rate was then administered to six animals. No significant change in QRS duration was noted at 1, 3, and 5 min intervals following physostigmine. Although no immediate antidotal effect of physostigmine on amitriptyline-induced QRS prolongation could be demonstrated, these results do not exclude a possible interaction between the membrane effects of the tricyclic antidepressants (and related agents) and the vagal branch of the autonomic nervous system.