Affecting more than 50 million people worldwide and with high global costs
annually, neurological disorders such as Alzheimer's disease (AD) and Parkinson’s
disease (PD) are a growing challenge all over the world. Globally, only in 2018, AD
costs reached an astonishing $ 1 trillion and, since the annual costs of AD are rapidly
increasing, the projections estimate that these numbers will double by 2030.
Considering the industrial perspective, the costs related to the development of new
drugs are extremely high when compared to the expected financial return. One of the
aggravating factors is the exorbitant values for the synthesis of chemical compounds,
hindering the process of searching for new drug candidates. In the last 10-year period,
an average of 20 to 40 new drugs were approved per year, representing a success rate
of less than 6%. However, the number of referrals for new drug orders and/or
applications remained at approximately 700 each year, reinforcing the difficulty in the
process of identifying and developing novel drugs. Regarding neurodegenerative
diseases, the FDA (USA) approved 53 new therapies in 2019, including 48 new
molecules and, from these, three are medicines and two are vaccines. The main drugs
recommended for the treatment of these disorders are included in the following classes:
Dopamine supplement (Levodopa), Monoamine oxidase (MAO) inhibitor (Selegiline,
Rasagiline), Dopamine agonist (Apomorphine, Pramipexole), and Acetylcholinesterase
inhibitor (Donepezil, Rivastigmine, Galantamine). Additionally, the current
pharmacological treatments are not able to cure these patients and considering the
etiological complexity and the prevalence of neurological disorders, scientists have a great challenge in exploring new therapies and new molecules to find an adequate and
viable treatment for these diseases. Clinical trials are essential in this process and thus,
this chapter describes the most important drugs that were targets of phase III and IV
clinical studies in the last five years, associated with the most common neurological
disorders worldwide, AD and PD. Information about mechanisms of action,
experimental studies in other diseases that support their use, and chemical structure of
the drugs are included in this chapter. Additionally, nature as a source of valuable
chemical entities for PD and AD therapeutics was also revised, as well as future
advances in the field regarding tracking new drugs to get successful results and critical
opinions in the research and clinical investigation.
Keywords: Acetylcholinesterase inhibitor, Clinical trials, FDA, Neurological disorders.