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Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice.

Abstract

The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN--a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four classical antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and valproate) in the mouse maximal electroshock seizure (MES) model. The results indicate that WIN (10 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test in mice. WIN (5 mg/kg) potentiated the anticonvulsant action of carbamazepine and valproate, but not that of phenytoin or phenobarbital in the MES test in mice. However, WIN administered alone and in combination with carbamazepine, phenytoin, phenobarbital and valproate significantly reduced muscular strength in mice in the grip-strength test. In the passive avoidance task, WIN in combination with phenobarbital, phenytoin and valproate significantly impaired long-term memory in mice. In the chimney test, only the combinations of WIN with phenobarbital and valproate significantly impaired motor coordination in mice. In conclusion, WIN enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test. However, the utmost caution is advised when combining WIN with classical antiepileptic drugs due to impairment of motor coordination and long-term memory and/or reduction of skeletal muscular strength that might appear during combined treatment.

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  • Publisher Full Text
  • Authors

    Luszczki JJ, Misiuta-Krzesinska M, Florek M, Tutka P, Czuczwar SJ

    Institution

    Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. jluszczki@yahoo.com

    Source

    Pharmacology, biochemistry, and behavior 98:2 2011 Apr pg 261-7

    MeSH

    Animals
    Anticonvulsants
    Avoidance Learning
    Benzoxazines
    Carbamazepine
    Drug Synergism
    Electroshock
    Male
    Memory, Long-Term
    Mice
    Morpholines
    Muscle Strength
    Naphthalenes
    Phenobarbital
    Phenytoin
    Psychomotor Performance
    Receptors, Cannabinoid
    Seizures
    Valproic Acid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21238473