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CNS drug development - lost in translation?

A Talevi1, C L Bellera, M Di Ianni

  • 1Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, Buenos Aires, Argentina. alantalevi@hotmail.com

Mini Reviews in Medicinal Chemistry
|March 17, 2012
PubMed

Insights

Developing central nervous system (CNS) drugs faces high failure rates due to pharmacokinetic challenges and unreliable preclinical models. This review explores strategies to improve CNS drug discovery and bioavailability.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Drug Development

Background:

  • Central nervous system (CNS) drug development has a high attrition rate.
  • Significant unmet medical needs exist in neuro-pharmacology.
  • Substantial investment is made in novel CNS drug treatments.

Purpose of the Study:

  • To overview the intrinsic difficulties in CNS drug development.
  • To highlight current efforts and modeling opportunities to overcome these limitations.
  • To emphasize approaches for improving CNS bioavailability.

Main Methods:

  • Review of existing literature on CNS drug development challenges.
  • Discussion of pharmacokinetic obstacles and preclinical test predictivity issues.
  • Exploration of modeling strategies for early CNS candidate recognition.

Main Results:

  • Identified pharmacokinetic barriers and lack of preclinical predictivity as key issues.
  • Highlighted multi-target directed ligands ("magic shotguns") as a potential strategy.
  • Discussed various approaches to enhance CNS bioavailability.

Conclusions:

  • Overcoming CNS drug development hurdles requires innovative approaches.
  • Modeling and improved bioavailability strategies are crucial for success.
  • Addressing these challenges can lead to more effective neuro-pharmacological treatments.

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