Isobolographic Analysis of Interaction for Three-Drug Combination of Carbamazepine, Phenobarbital and Topiramate in the Mouse Maximal Electroshock-Induced Seizure Model.

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  • Author(s): Luszczki JJ;Luszczki JJ
  • Source:
    Pharmacology [Pharmacology] 2016; Vol. 97 (5-6), pp. 259-64. Date of Electronic Publication: 2016 Feb 25.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Karger Country of Publication: Switzerland NLM ID: 0152016 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1423-0313 (Electronic) Linking ISSN: 00317012 NLM ISO Abbreviation: Pharmacology Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel (Switzerland) : Karger,
    • Subject Terms:
      Anticonvulsants/*therapeutic use ; Carbamazepine/*therapeutic use ; Fructose/*analogs & derivatives ; Phenobarbital/*therapeutic use ; Seizures/*drug therapy; Animals ; Disease Models, Animal ; Drug Interactions ; Drug Therapy, Combination ; Electroshock ; Fructose/therapeutic use ; Male ; Mice ; Topiramate
    • Abstract:
      Background/aims: To characterize the anticonvulsant effects of a combination of 3 antiepileptic drugs (AEDs; i.e. carbamazepine (CBZ), phenobarbital (PB) and topiramate (TPM)) at the fixed-ratio of 1:1:1 in the mouse maximal electroshock (MES)-induced seizure model.
      Methods: Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Type I isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to analyze the 3-drug combination.
      Results: In the mouse MES model, all the studied AEDs (i.e., CBZ, PB and TPM) administered singly had their DRRCs parallel to each other. With type I isobolography for parallel DRRCs, a combination of CBZ, PB and TPM at the fixed-ratio of 1:1:1 exerted supra-additive (synergistic) interaction in the mouse MES model.
      Conclusions: Synergistic interaction among CBZ, PB and TPM at the fixed-ratio of 1:1:1 against MES-induced seizures is worthy of consideration in further clinical settings. All detailed calculations required to perform type I isobolographic analysis for the 3-drug combination were presented.
      (© 2016 S. Karger AG, Basel.)
    • Accession Number:
      0 (Anticonvulsants)
      0H73WJJ391 (Topiramate)
      30237-26-4 (Fructose)
      33CM23913M (Carbamazepine)
      YQE403BP4D (Phenobarbital)
    • Publication Date:
      Date Created: 20160225 Date Completed: 20161213 Latest Revision: 20181202
    • Publication Date:
      20240829
    • Accession Number:
      10.1159/000444452
    • Accession Number:
      26910763