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Principles of Safety Pharmacology pp 83–113Cite as

CNS Adverse Effects: From Functional Observation Battery/Irwin Tests to Electrophysiology

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 229))

Abstract

This chapter describes various approaches for the preclinical assessment of drug-induced central nervous system (CNS) adverse effects. Traditionally, methods to evaluate CNS effects have consisted of observing and scoring behavioral responses of animals after drug is administered. Among several behavioral testing paradigms, the Irwin and the functional observational battery (FOB) are the most commonly used assays for the assessment of CNS effects. The Irwin and FOB are considered good first-tier assays to satisfy the ICH S7A guidance for the preclinical evaluation of new chemical entities (NCE) intended for humans. However, experts have expressed concern about the subjectivity and lack of quantitation that is derived from behavioral testing. More importantly, it is difficult to gain insight into potential mechanisms of toxicity by assessing behavioral outcomes. As a complement to behavioral testing, we propose using electrophysiology-based assays, both in vivo and in vitro, such as electroencephalograms and brain slice field-potential recordings. To better illustrate these approaches, we discuss the implementation of electrophysiology-based techniques in drug-induced assessment of seizure risk, sleep disruption, and cognitive impairment.

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Authors and Affiliations

  1. Global Safety Pharmacology, AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA, 02451, USA

    Carlos Fonck, Alison Easter, Mark R. Pietras & Russell A. Bialecki

  2. Biogen Idec, 14 Cambridge Center, Cambridge, MA, 02142, USA

    Alison Easter

Authors
  1. Carlos Fonck
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  2. Alison Easter
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  3. Mark R. Pietras
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  4. Russell A. Bialecki
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Correspondence to Russell A. Bialecki .

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Editors and Affiliations

  1. Drug Safety Sciences, Johnson & Johnson PR&D, Raritan, New Jersey, USA

    Michael K. Pugsley

  2. Cardiovascular Division, Faculty of Life Sciences & Medicine, St Thomas' Hospital, King's College London, Rayne Institute, London, United Kingdom

    Michael J Curtis

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Fonck, C., Easter, A., Pietras, M.R., Bialecki, R.A. (2015). CNS Adverse Effects: From Functional Observation Battery/Irwin Tests to Electrophysiology. In: Pugsley, M., Curtis, M. (eds) Principles of Safety Pharmacology. Handbook of Experimental Pharmacology, vol 229. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46943-9_4

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