Ergot alkaloids. New ergolines as selective dopaminergic stimulants

Article abstract of DOI:10.1021/jm00206a007

A new two-step sequence for the epimerization of methyl dihydrolysergate at C-8 leading to methyl dihydroisolysergate is presented. The latter compound was used as a starting material for the sythesis of various ergolines, of which (5R,8R,10R)-8-(cyanomethyl)-6-methylergoline is a very strong and long-lasting central dopaminergic agent. Furthermore, it was found that some 8-(arylthiomethyl)-6-methylergolenes are not able to induce apomorphine-like stereotyped behavior in normal rats but a remarkable activity in rats unilaterally lesioned by 6-OH-DA in the nigrostriatal region. A compound and (5R,8R)-8-(2-pyridyl)thiomethyl]-6-methylergolene were further tested for their ability to inhibit ovum implantation and to depress serum prolactin levels in rats. Their potency was evaluated in comparison with (5R,8S,10R)-8(cyanomethyl)-6-methylergolines and 2-bromo-α-ergocryptine as standards.