COMPARATIVE STUDY ON THE SEROTONIN ANTAGONISM OF AMIDE DERIVATIVES OF LYSERGIC ACID AND OF ERGOT ALKALOIDS

¹ Pharmacological Laboratory, Sandoz Ltd., Baste, Switzerland

The quantitative and qualitative characteristics of the 5-HT antagonism of a large number of natural and semi-synthetic "ergot derivatives" have been studied on the isolated rat uterus. Within a group of about twenty amide derivatives of lysergic acid, more or less closely related to LSD-25 from a chemical point of view, none reached the degree of activity and specificity of this well known serotonin inhibitor. The substance next to LSD in antiserotonin potency was the mono-amylamide of lysergic acid. Three stereoisomers of LSD were practically ineffective. This was also true for Lumi-LSD, whereas dihydro-LSD still maintained 50 per cent of the activity of the unsaturated original product. Similar comparative studies with the whole series of natural ergot alkaloids and their respective hydrogenated derivatives revealed only moderate degrees of serotonin antagonism. The semi-synthetic alkaloid methylergonovine, however, proved to be quite an effective and specific inhibitor. Substances with antiserotonin activities higher than LSD were found within a group of LSD derivatives with different substitutions on the ring structure of lysergic acid. The most potent compound thus far studied was the 1-methyl-2-bromo lysergic acid diethylamide.

This article has been cited by other articles:

				A. L. Scherbel and J. W. Harrison Response To Serotonin and Its Antagonists in Patients With Rheumatoid Arthritis and Related Diseases*{dagger} Angiology, February 1, 1959; 10(1): 29 - 33. [PDF]

				R. P. Bircher Vascular Dynamics Angiology, February 1, 1959; 10(1): 81 - 83. [PDF]