Dopaminergic properties of mesulergine (CU 32-085) and its metabolites

Mesulergine, an 8-alpha-aminoergoline, is now proven to be of utility in the clinic as an antiparkinsonian drug. However, the molecule itself shows in vitro and in vivo antidopaminergic properties. Mesulergine is rapidly metabolized into several pharmacologically active DA agonists. The influence of mesulergine on central DA metabolism in rats is dependent on the route of drug administration. It was possible to determine the different metabolites of this drug in plasma as well as in rat striatum. A correlation between the actual present concentration of the parent drug and DAergic metabolites and the net action on striatal DA metabolism was found. It may be concluded that mesulergine itself lacks DAergic activity but occupies DA receptors and is very rapidly metabolized into potent DA agonists.