Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice.
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.
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. jluszczki@yahoo.com
Jarogniew J
JJ
Luszczki
Marta
M
Misiuta-Krzesinska
Magdalena
M
Florek
Piotr
P
Tutka
Stanislaw J
SJ
Czuczwar
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001362:Avoidance Learning / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage* / Q000633:toxicity; D063386:Cannabinoid Receptor Agonists; D002220:Carbamazepine / Q000008:administration & dosage; D004357:Drug Synergism; D004597:Electroshock; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage* / Q000633:toxicity; D053580:Muscle Strength / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage* / Q000633:toxicity; D010634:Phenobarbital / Q000008:administration & dosage; D010672:Phenytoin / Q000008:administration & dosage; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D014635:Valproic Acid / Q000008:administration & dosage
D000927:Anticonvulsants; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D002220:Carbamazepine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital