1-Methyl-8 β-carbobenzyloxy-aminomethyl-10 α-ergoline, a Potent and Long-lasting 5-Hydroxytryptamine Antagonist

Abstract

IT has been proved that derivatives of 6-methylergoline and 6-methylergolene specifically antagonize 5HT. In this group of substances the more active are d-lysergic acid diethylamide (LSD₂₅) and 1-methyl-d-lysergic acid butanolamide (UML₄₉₁). We now report a potent and exceptionally long-lasting 5HT antagonist, namely the 1-methyl-8 β-carbobenzyloxy-aminomethyl-10 α-ergoline (MCE), a new compound synthesized in our laboratories¹, the structural formula of which is: Its LD₅₀ is 85 mg/kg intraperitoneally and 430 mg/kg per os in mice; more than 800 mg/kg per os in rats; and about 20 mg/kg intravenously in rabbits. This new compound has been tested for its pharmacological actions both in vitro and in vivo. The results obtained in vitro are summarized in Table 1. All the aqueous solutions were made with the aid of maleic or ascorbic acid in slight excess. When administered per os the compound was suspended in 5 per cent gum acacia.