Development of Prodrugs for Treatment of Parkinson‘s Disease: New Inorganic Scaffolds for Blood–Brain Barrier Permeation

The treatment of Parkinson's disease (PD) has not been consistently modified for more than 60 years. L-DOPA, the blood-brain barrier permeable precursor prodrug of dopamine, is to date the only effective therapy on the market. However, it is well known that prolonged treatment with L-DOPA leads to several side effects, which may affect the patient's life expectancy (i.e., the wearing-off phenomenon, on-off fluctuations, and dyskinesia). For this reason, modifications, and supplements to L-DOPA treatment have been and are being studied, which, however, have not yet resulted in a valid alternative to the cornerstone drug. This review aims to summarize the main formulations currently in use for PD treatment, explaining advantages and disadvantages for each class. The attention will be focused on the promising prodrug concept, aimed at finding a suitable L-DOPA substitute with improved pharmacokinetic behavior. In this respect, new potential candidates which show interesting properties for the intended scope, the so-called dicarba-closo-dodecaboranes(12) (carboranes), will be discussed. Carboranes are inorganic molecular icosahedral boron-carbon clusters with 12 vertices and 20 deltahedral faces. They have been extensively studied for applications in medicine as potential pharmacophores, reagents in boron neutron capture therapy (BNCT) and radiotherapy. Here, we discuss them as inorganic scaffolds for dopamine delivery at the central nervous system (CNS) level.