Development of benztropine-based DAT blockers for Parkinson's disease interventions: A biologic and synthetic...

Parkinson's disease is considered a neurodegenerative brain affection where the substantia nigra, a group of dopamine producer neurons are eliminated and hence, dopamine levels go to dangerous lower levels. With this molecule limited, an imbalance in neurotransmitters is set, a decreased neurological activity is set affecting the motion and several communication pathways. The most recognized outcome lies in the motor cortex, which is characterized by different motor symptoms such as bradykinesia, rigidity, uncontrollable tremors, imbalance, stiffness, and sudden slowness for several corporal movements. Since this is an incurable disease, pharmacological studies focus on the symptom's elimination and palliative care, researching on dopaminergic transporters (DAT) blockage to enhance the action of exogenous dopamine by stopping dopamine reabsorption and allowing correct neurotransmission. Several chemical structures have been evaluated and one of the most popular, benztropine, recently has been synthetically and biologically studied by several research groups. In this document we briefly discuss the disease to guide the reader in the journey of several research groups that have selected dopamine receptors and channels as targets for drug development, broadly focused on the synthesis and action mechanism of benztropine and analogs for Parkinson's disease treatment, in order to showcase the potential of molecules that seem obsolete when chemical modification is on reach and the power of the chemical tools for their modification.