OBSERVATIONS ON THE PHARMACOLOGICAL ACTIONS OF THE ISOMERS OF ATROPINE

¹ Department of Pharmacology, University of Michigan, Ann Arbor, Michigan

The central and peripheral actions of d-and l-hyoscyamine were investigated using rats, dogs and monkeys. Six different measures of central nervous system activity were used: (1) spontaneous EEG in acute dogs, (2) the mean duration of EEG arousal to stimulation of the sciatic nerve in the acute dogs, (3) the spontaneous EEG in monkeys with chronically implanted electrodes, (4) EEG arousal to various afferent stimuli in monkeys with chronically implanted electrodes, (5) gross monkey behavior, and (6) rat conditioned avoidance behavior. Two different measures of peripheral cholinergic muscarinic activity were used: (1) the depressor responses in arterial blood pressure to methacholine, and (2) the spontaneous heart rate in unanesthetized dogs immobilized with decamethonium.

In all of these tests of both central and peripheral activity l-hyoscyamine was more potent than its d-isomer. The potency ratios of the two isomers varied from 8 to no more than 50 times depending in part upon the purity of the sample of d-hyoscyamine as well as the test preparation.