title: Effects of WIN 55,212-2 (a synthetic cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.
abstract: The purpose of this study was to determine the influence of WIN 55,212-2 mesylate (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various second- and third-generation antiepileptic drugs (i.e., gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin and tiagabine) in the mouse 6 Hz-induced psychomotor seizure model. Psychomotor seizures were evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes. Additionally, total brain antiepileptic drug concentrations were measured. Results indicate that WIN (5 mg/kg, administered i.p.) significantly potentiated the anticonvulsant action of gabapentin (P < 0.05) and levetiracetam (P < 0.01), but not that of lacosamide, oxcarbazepine, pregabalin or tiagabine in the mouse psychomotor seizure model. Moreover, WIN (2.5 mg/kg) had no significant effect on the anticonvulsant activity of all tested antiepileptic drugs in the 6 Hz test in mice. Measurement of total brain antiepileptic drug concentrations revealed that WIN (5 mg/kg) had no impact on gabapentin or levetiracetam total brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse 6Hz model. In conclusion, WIN in combination with gabapentin and levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in the mouse psychomotor seizure model.
authors.affiliation: Department of Public Health, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florek-Luszczki
authors.affiliation: Department of Pathophysiology, Medical University, Ceramiczna 1, PL 20-150 Lublin, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wlaz
authors.affiliation: Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Zagaja
authors.affiliation: Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Andres-Mach
authors.affiliation: Department of Pathophysiology, Medical University, Ceramiczna 1, PL 20-150 Lublin, Poland.
authors.forename: Maria W
authors.initials: MW
authors.lastname: Kondrat-Wrobel
authors.affiliation: Department of Pathophysiology, Medical University, Ceramiczna 1, PL 20-150 Lublin, Poland; Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland. Electronic address: jarogniew.luszczki@gmail.com.
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D018737:Hand Strength; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009048:Motor Skills / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
keywords: 6Hz psychomotor seizure model; Antiepileptic drugs; Cannabinoids; Drug interactions; WIN 55,212-2 mesylate