Acute and chronic treatment with moclobemide, a reversible MAO-inhibitor, potentiates the antielectroshock activity of conventional antiepileptic drugs in mice.

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  • Author(s): Borowicz-Reutt KK;Borowicz-Reutt KK; Banach M; Banach M
  • Source:
    Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2021 Feb; Vol. 201, pp. 173110. Date of Electronic Publication: 2021 Jan 12.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0367050 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5177 (Electronic) Linking ISSN: 00913057 NLM ISO Abbreviation: Pharmacol Biochem Behav Subsets: MEDLINE
    • Publication Information:
      Publication: Tarrytown, NY : Elsevier
      Original Publication: Phoenix, N. Y. Ankho International, ltd.
    • Subject Terms:
      Electroshock*; Anticonvulsants/*administration & dosage ; Carbamazepine/*administration & dosage ; Moclobemide/*administration & dosage ; Monoamine Oxidase Inhibitors/*administration & dosage ; Phenobarbital/*administration & dosage ; Phenytoin/*administration & dosage ; Seizures/*drug therapy ; Valproic Acid/*administration & dosage; Animals ; Brain/metabolism ; Carbamazepine/metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Synergism ; Epilepsy/drug therapy ; Female ; Male ; Memory, Long-Term/drug effects ; Mice ; Moclobemide/adverse effects ; Monoamine Oxidase Inhibitors/adverse effects ; Motor Activity/drug effects ; Phenobarbital/metabolism ; Phenytoin/metabolism ; Valproic Acid/metabolism
    • Abstract:
      Background: Due to enhancing serotonergic and noradrenergic neurotransmission, moclobemide may influence seizure phenomena. In this study, we examined the effect of both acute and chronic treatment with moclobemide on seizures and the action of first-generation antiepileptic drugs: valproate, carbamazepine, phenobarbital and phenytoin.
      Methods: The effect of moclobemide on seizures was assessed in the electroconvulsive threshold test, while its influence on antiepileptic drugs was estimated in the maximal electroshock test in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay.
      Results: Given acutely, moclobemide at 62.5 and 75 mg/kg increased the electroconvulsive threshold. In contrast, chronic treatment with moclobemide up to 75 mg/kg did not influence this parameter. Acute moclobemide applied at subthreshold doses (up to 50 mg/kg) enhanced the antielectroshock effects of carbamazepine, valproate and phenobarbital. Chronic moclobemide (37.5-75 mg/kg) increased the action of all four antiepileptic drugs. All revealed interactions, except these between moclobemide and phenobarbital, seem to have pharmacokinetic nature, because the antidepressant drug, either in acute or in chronic treatment, increased the brain concentrations of respective antiepileptic drugs. In terms of undesired neurotoxic effects, acute and chronic moclobemide, antiepileptic drugs, and their combinations did not produce significant motor or long-term memory impairment.
      Conclusions: Acute and chronic therapy with moclobemide can increase the effectiveness of some antiepileptic drugs against the maximal electroshock test. In mice, this effect was, at least partially, due to pharmacokinetic interactions. So far as the results of experimental studies can be transferred to clinical conditions, moclobemide seems safe for the application in patients with epilepsy and depression. Possibly, in the case of certain antiepileptic drugs combined with moclobemide, their doses should be adjusted downwards.
      (Copyright © 2021 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Antiepileptic drugs; Electroshock maximal; Moclobemide; Pharmacodynamic interaction; Pharmacokinetic interaction
    • Accession Number:
      0 (Anticonvulsants)
      0 (Monoamine Oxidase Inhibitors)
      33CM23913M (Carbamazepine)
      614OI1Z5WI (Valproic Acid)
      6158TKW0C5 (Phenytoin)
      PJ0Y7AZB63 (Moclobemide)
      YQE403BP4D (Phenobarbital)
    • Publication Date:
      Date Created: 20210114 Date Completed: 20210810 Latest Revision: 20210810
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.pbb.2021.173110
    • Accession Number:
      33444604