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Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish.

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  • معلومة اضافية
    • المصدر:
      Publisher: Doku Sayō Kenkyūkai Country of Publication: Japan NLM ID: 7805798 Publication Model: Print Cited Medium: Internet ISSN: 1880-3989 (Electronic) Linking ISSN: 03881350 NLM ISO Abbreviation: J Toxicol Sci Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Sapporo, Japan Doku Sayō Kenkyūkai
    • الموضوع:
      Drug Discovery*; Drug Evaluation, Preclinical/*methods ; High-Throughput Screening Assays/*methods ; Motor Activity/*drug effects ; Seizures/*chemically induced ; Toxicology/*methods ; Zebrafish/*physiology; Animals ; Drug-Related Side Effects and Adverse Reactions ; Photic Stimulation
    • نبذة مختصرة :
      As drug-induced seizures have severe impact on drug development, evaluating seizure induction potential of candidate drugs at the early stages of drug discovery is important. A novel assay system using zebrafish has attracted interest as a high throughput toxicological in vivo assay system, and we tried to establish an experimental method for drug-induced seizure liability on the basis of locomotor activity in zebrafish. We monitored locomotor activity at high-speed movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed seizure liability potential in some drugs using locomotor activity. However this experimental procedure was not sufficient for predicting seizures because the potential of several drugs with demonstrated seizure potential in mammals was not detected. We, therefore, added other parameters for locomotor activity such as extending exposure time or conducting flashlight stimulation (10 Hz) which is a known seizure induction stimulus, and these additional parameters improved seizure potential detection in some drugs. The validation study using the improved methodology was used to assess 52 commercially available drugs, and the prediction rate was approximately 70%. The experimental protocol established in this present study is considered useful for seizure potential screening during early stages of drug discovery.
    • الموضوع:
      Date Created: 20140725 Date Completed: 20150604 Latest Revision: 20190911
    • الموضوع:
      20221213
    • الرقم المعرف:
      10.2131/jts.39.579
    • الرقم المعرف:
      25056783