Document Detail

Challenges in the search for drugs to treat central nervous system disorders.
MedLine Citation:
PMID:  19182069     Owner:  NLM     Status:  MEDLINE    
The history of drug discovery spans approximately 200,000 years. For much of this time, the identification of therapeutic agents was empirical, with the shift to a more hypothesis-driven approach occurring in the late 19th century. Since then, the objective has changed from identifying an active drug and its mechanism of action to determining therapeutic potential only after identifying drug-like compounds that interact with a target site. Although the emphasis on target identification, or "targephilia," has yielded novel drugs, overall it appears to have slowed the drug discovery process, especially for compounds used in treating central nervous system (CNS) disorders. This is because the "targephilic" approach requires a good understanding of target physiology and its integration with the target organ, with a hierarchical integration from in vitro cellular and functional tissue studies to animal models that reasonably predict human responses. Because the majority of CNS drugs were discovered empirically, drug discovery in this area appears less amenable to target-based approaches than it seems for other types of therapeutics. Improving the success rate in CNS drug discovery requires a more pharmacometric-based approach, with a renewed emphasis on defining basic CNS function in intact animals and a more systematic in vivo screening of novel structures. Efforts must also be directed toward defining the sites of action of existing CNS drugs to aid in the design of second-generation agents with improved efficacy and safety.
S J Enna; M Williams
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Publication Detail:
Type:  Journal Article     Date:  2009-01-30
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  329     ISSN:  1521-0103     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-05-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  404-11     Citation Subset:  IM    
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
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MeSH Terms
Central Nervous System Agents / chemistry,  pharmacology*,  therapeutic use
Central Nervous System Diseases / drug therapy*,  genetics,  metabolism
Disease Models, Animal
Drug Design*
Small Molecule Libraries
Reg. No./Substance:
0/Central Nervous System Agents; 0/Small Molecule Libraries

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