The influence of physostigmine on respiratory and circulatory changes caused by overdoses of orphenadrine or imipramine in the rat.

Orphenadrine or imipramine were given intravenously as an infusion to spontaneously breathing, anaesthetized rats until respiratory arrest, the primary cause of death for both drugs. Intravenous injections of physostigmine did not prolong survival. Artificial ventilation prolonged survival for orphenadrine and imipramine by about a factor 3 and the rats died from cardiogenic shock. The cardiotoxic properties of orphenadrine and imipramine express themselves as a progressing disturbance in stimulus formation and conduction, a decrease in dP/dt max and increase in left ventricular end-diastolic pressure and a decrease in cardiac output caused by the progressing decrease of heart rate. An intravenous injection of physostigmine did not prolong survival and had no favourable effect on the cardiotoxicity caused by orphenadrine and imipramine. Although physostigmine may be useful in the treatment of the anticholinergic syndrome it has, at least in the rat, no favourable effect on the respiratory insufficiency, due to overdoses of orphenadrine and imipramine. Moreover it is not effective in antagonizing the cardiotoxic effects of orphenadrine or imipramine.