Research Areas and Methods

Our first aim was to select a suitable candidate serving as water soluble pro-drug of Levodopa (LD) (3). Small and short-term clinical pharmacokinetic studies were used for development steps. One candidate (Gly-Dopa (3)) showed a reduced absolute bioavailability and was postponed in favor of Penta-Dopa (3), our development candidate. Then we studied the influence of oral doses and dose distributions of two decarboxylase inhibitors (DC-I), i.e. benserazide (3) and carbidopa (3) on LD plasma levels. The observation of a sudden effect of oral DC-I on LD levels and the interactions with the catechol-O-methyl-transferase (COMT) inhibitor Opicapone®(3) drew our attention to a new treatment principle. By chance, AbbVie´s product Pro-Duodopa®(7) containing Foslevodopa (FLD) (3) and Foscarbidopa (FCD) (3) entered the EU market. The by far further developed FLD (compared to our Penta-Dopa) presents an ideal opportunity to be integrated into our invention, now designed as BRM-203 (6). This is feasible because FLD is a patent-free compound.