Examining US FDA Approved Central Nervous Drugs from 2015-2023

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2024-11-22

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Title: Examining US FDA Approved Central Nervous System Drugs from 2015-2023 Vincent Tran, Cierra Fujimoto, Dianqing Sun Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hawaii 96720, United States Purpose: Since 2015, the US Food and Drug Administration (FDA) has approved 400 new chemical entity and biologic drugs with approximately 11 percent of these drugs falling within the central nervous system (CNS) category. CNS drugs mediate the functioning of the brain and spinal cord, and also regulate the human body’s physical and mental well-being. The purpose of this study is to conduct a comprehensive analysis and overview of the medicinal and physicochemical properties, pharmacokinetic (PK) profiles, and clinical applications of these FDA approved CNS drugs from 2015-2023. Methods: This data analysis was conducted using new molecular entity and new therapeutic biological product approval online resources provided by the US FDA’s Center for Drug Evaluation and Research (CDER). Literature review was performed by searching online databases such as Lexicomp and prescribing information document. Physicochemical properties were obtained from ChemSpider and Chemfinder database. Lipinski’s Rule of Five (molecular weight, hydrogen bond acceptor, hydrogen bond donor, and LogP) was used to assess the oral bioavailability, routes of administration, and rationalize their clinical applications of these CNS agents. Results: As of September 2023, the US FDA has approved 400 new chemical entity and therapeutic biologic drugs since 2015 with a total of 44 new CNS drug approvals. Among the CNS drug classes, the highest number of new CNS drugs approvals was for mental disorders (22.7%), followed by migraines (20.5%), anti-seizure (11.4%), sleeping disorders (9.1%), amyotrophic lateral sclerosis (ALS) (6.8%), multiple sclerosis (6.8%), Parkinson’s disease (6.8%), Alzheimer’s disease (4.5%), neuromyelitis optica spectrum disorder (4.5%), Huntington’s disease (2.3%), opioid withdrawal (2.3%), and sedatives (2.3%). Chemically, there are 29 small molecules, 11 biologic monoclonal antibodies (mAbs), 1 antisense oligonucleotide, and 3 combination therapy products. With regard to drug characteristics of these 29 small molecule CNS agents, >70% of these compounds have polar surface area (PSA) values of < 90 Å2, with favorable blood-brain barrier (BBB) penetration profiles; and 19 drugs have logP values ranging from 2 to 5; and 5 drugs had a logP of >5 with more lipophilic profiles. Furthermore, 20 drugs have a basic functionality, with 8 drugs being neutral and 4 being weakly acidic under physiological conditions. Detailed physicochemical properties, PK parameters, and clinical indications, and recommended dosages of these CNS medications will be presented. Conclusion: From 2015-2023, remarkable medicine advances have been made with 400 total new drug approvals from the FDA. Among them, 44 drugs fall within the CNS category, remaining as one of the top 3 drug approval category following oncology and infectious disease. From a medicinal chemistry standpoint, to enable the BBB penetration, most of these CNS approved drugs are lipophilic and basic or neutral as the acidic functionality is not well tolerated due to the negatively charged form under physiological condition. This work serves as a valuable resource and medication information for clinicians and drug discovery researchers.

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http://rightsstatements.org/vocab/InC-EDU/1.0/

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UH Hilo DKICP

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