The Action of Toxic Doses of Atropine on the Central Nervous System

Abstract

Scattered data concerning stimulation and depression of the central nervous system following the administration of atropine are both numerous and contradictory. Albertoni 1 reported that atropine in doses from 2–10 mg per kg increases the electrical excitability of the motor cortex and facilitates the production of epileptiform seizures following stimulation of motor areas in dogs and monkeys, and stated that fatal or nearly fatal doses exert depressant or paralysant effects (terminating in paralysis of the limbs and respiratory muscles) without previous stimulation. Fraser 2 and Issekutz 3 described after initial depression the appearance of strychninelike convulsions in frogs.

Joel, 4 Garcia, 5 Silver 6 and Friedberg 7 reported that the combination of atropine or hyoscyamine or scopolamine with morphine, ether, sodium phenobarbital or pernoston enhances the action of these narcotics. These authors used nearly anesthetic doses of the aliphatic depressants and supplemented these with doses from 25 to 50 mg of atropine per kg, immediately or a few minutes later. It is significant that Friedberg states that the synergism does not occur if the atropine is given one-half hour after injection of the barbiturates. All these experiments were carried out in rodents and it is obvious that a possible shock-producing effect of atropine given immediately on top of a sizeable dose of a central depressant, was not eliminated.

Very recently Schweitzer and Wright 8 have shown that 0.5–3.0 mg of atropine per kg depress the knee jerk owing to a central action and that these doses do not markedly antagonize either the excitatory action of physostigmine or the characteristic central inhibition produced by larger doses of acetylcholine.

The following experiments were carried out to study separately the stimulant and depressant actions of atropine and subject them to pharmacodynamic analysis. This was found possible only if large doses of this drug were employed.