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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.
Pharmacol Biochem Behav 2015; 130:53-8PB

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+Show Affiliations

Department of Public Health, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland.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.Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, PL 20-950 Lublin, Poland.Department of Pathophysiology, Medical University, Ceramiczna 1, PL 20-150 Lublin, Poland.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.

Pub Type(s)

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

Language

eng

PubMed ID

25592741

Citation

Florek-Luszczki, Magdalena, et al. "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." Pharmacology, Biochemistry, and Behavior, vol. 130, 2015, pp. 53-8.
Florek-Luszczki M, Wlaz A, Zagaja M, et al. 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. Pharmacol Biochem Behav. 2015;130:53-8.
Florek-Luszczki, M., Wlaz, A., Zagaja, M., Andres-Mach, M., Kondrat-Wrobel, M. W., & Luszczki, J. J. (2015). 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. Pharmacology, Biochemistry, and Behavior, 130, pp. 53-8. doi:10.1016/j.pbb.2015.01.003.
Florek-Luszczki M, et al. 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. Pharmacol Biochem Behav. 2015;130:53-8. PubMed PMID: 25592741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Florek-Luszczki,Magdalena, AU - Wlaz,Aleksandra, AU - Zagaja,Mirosław, AU - Andres-Mach,Marta, AU - Kondrat-Wrobel,Maria W, AU - Luszczki,Jarogniew J, Y1 - 2015/01/13/ PY - 2014/10/22/received PY - 2014/12/27/revised PY - 2015/01/07/accepted PY - 2015/1/17/entrez PY - 2015/1/17/pubmed PY - 2015/12/24/medline KW - 6Hz psychomotor seizure model KW - Antiepileptic drugs KW - Cannabinoids KW - Drug interactions KW - WIN 55,212-2 mesylate SP - 53 EP - 8 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 130 N2 - 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. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/25592741/Effects_of_WIN_55212_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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(15)00005-2 DB - PRIME DP - Unbound Medicine ER -