Central and Peripheral Effects of Muscarinic Cholinergic Blocking Agents in Man

Abstract

The effects of scopolamine, methscopolamine, atropine, andl-hyoscyamine were compared in patient-volunteers without premedication, on an equimolar basis on: (1) visually evoked responses (VER), spontaneous EEG activity, and sedation as an index of a central nervous system action; (2) spontaneous heart rate; and (3) dilute citric acid-induced salivary flow. Scopolamine significantly depressed the early components of the VER, which correlated with the state of wakefulness, and caused simultaneous changes in thealpharhythm of the EEG towards relaxation or sedation. Atropine,l-hyoscyamine, and methscopolamine had no significant effect on the VER and EEG in equimolar doses. Methscopolamine caused the greatest increase in heart rate, followed by atropine and scopolamine, each of which increased the heart rate within two minutes. The scopolamine-induced increase lasted only about 10 minutes, whereas the effect of atropine,l-hyoscyamine, and methscopolamine continued for 30 minutes or more. Ten to 30 minutes following scopolamine bradycardia was observed. Equimolar doses ofl-hyoscyamine were more effective than atropine in increasing the heart rate. With regard to blockade of salivary flow the following order of effectiveness was obtained: methscopolamine > scopolamine >l-hyoscyamine > atropine. A dose ofl-hyoscyamine consisting of half the dose of atropine produced about the same effects, indicating the relative ineffectiveness of thed-hyoscyamine fraction of atropine.