RESEARCH PAPER
WIN 55,212-2 mesylate (a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) elevates the threshold for maximal electroshock-induced seizures in mice
 
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1
Department of Pathophysiology, Medical University, Lublin, Poland
 
2
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
 
3
Department of Neurology, UC Davis School of Medicine,Sacramento, USA
 
 
Corresponding author
Jarogniew J. Łuszczki   

Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
 
 
J Pre Clin Clin Res. 2009;3(2):110-113
 
KEYWORDS
ABSTRACT
The aim of this study was to determine the eff ect of WIN 55,212-2 mesylate (a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) on the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions were produced in mice by means of a current (sine-wave, 50 Hz, maximum 500 V, strength 4 - 14 mA, via ear-clip electrodes, 0.2-s stimulus duration, tonic hind limb extension taken as the endpoint). WIN 55,212-2 mesylate administered systemically (i.p.), 20 min before the MEST test, at doses of 5 and 10 mg/kg, did not alter the threshold for maximal electroconvulsions in mice. In contrast, WIN 55,212-2 mesylate at doses of 15 and 20 mg/kg signifi cantly elevated the threshold for maximal electroconvulsions in mice (P<0.05 and P<0.001). Linear regression analysis of WIN 55,212-2 mesylate doses and their corresponding threshold increases allowed for the determination of threshold increasing doses by 20% and 50% (TID20 and TID50 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 and TID50 values for WIN 55,212-2 mesylate were 6.3 and 17.2 mg/kg, respectively. Based on this preclinical study, one can ascertain that WIN 55,212- 2 mesylate dose-dependently increased the threshold for MEST-induced seizures, suggesting the anticonvulsant action of the compound in this seizure model in mice
 
REFERENCES (20)
1.
Glantz SA, Slinker BK: Primer of applied regression and analysis of variance 2nd ed), McGraw-Hill Inc., New York 2001.
 
2.
Hayase T, Yamamoto Y, Yamamoto K: Protective eff ects of cannabinoid receptor agonists against cocaine and other convulsant-induced toxic behavioural symptoms. J Pharm Pharmacol 2001, 53, 1525-1532.
 
3.
Koda S, Takeda S, Onimaru H, Akada S, Sakamoto A: Cannabinoid suppressed bicuculline-induced convulsion without respiratory depression in the brainstem-spinal cord preparation from newborn rats. Biomed Res 2005, 26, 241-247.
 
4.
Litchfi eld JT, Wilcoxon F: A simplifi ed method of evaluating dose-eff ect experiments. J Pharmacol Exp Ther 1949, 96, 99-113.
 
5.
Loscher W, Fassbender CP, Nolting B: The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res 1991, 8, 79-94.
 
6.
Loscher W, Wauquier A: Use of animal models in developing guiding principles for polypharmacy in epilepsy. Epilepsy Res 1996 (Suppl.),11, 61-65.
 
7.
Łuszczki JJ, Antkiewicz-Michaluk L, Czuczwar SJ: Isobolographic analysis of interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and four conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Eur J Pharmacol 2009, 602, 298- 305.
 
8.
Łuszczki JJ, Czuczwar SJ: How signifi cant is the diff erence between drug doses infl uencing the threshold for electroconvulsions? Pharmacol Rep 2005, 57, 782-786.
 
9.
Łuszczki JJ, Czuczwar SJ: Isobolographic characterization of interactions between vigabatrin and tiagabine in two experimental models of epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 2007, 31, 529- 538.
 
10.
Łuszczki JJ, Dudra-Jastrzębska M, Andres-Mach M, Czernecki R, Barcicka-Kłosowska B, Misiuta-Krzesińska M, Zwoliński J, Filip D: Stiripentol in a dose-dependent manner elevates the threshold for maximal electroshock-induced seizures in mice. J Pre-Clin Clin Res 2007, 1, 155-157.
 
11.
Łuszczki JJ, Ratnaraj N, Patsalos PN, Czuczwar SJ: Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Naunyn Schmiedebergs Arch Pharmacol 2006, 373, 169-181.
 
12.
Łuszczki JJ, Ratnaraj N, Patsalos PN, Czuczwar SJ: Isobolographic and behavioral characterizations of interactions between vigabatrin and gabapentin in two experimental models of epilepsy. Eur J Pharmacol 2008, 595, 13-21.
 
13.
Naderi N, Aziz Ahari F, Shafaghi B, Najarkolaei AH, Motamedi F: Evaluation of interactions between cannabinoid compounds and diazepam in electroshock-induced seizure model in mice. J Neural Transm 2008, 115, 1501-1511.
 
14.
Rizzo V, Ferraro G, Carletti F, Lonobile G, Cannizzaro C, Sardo P: Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat. Neurosci Lett 2009, 462, 135-139.
 
15.
Shen M, Thayer SA: Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture. Mol Pharmacol 1999, 55, 8-13.
 
16.
Shen M, Thayer SA: The cannabinoid agonist Win55,212-2 inhibits calcium channels by receptor-mediated and direct pathways in cultured rat hippocampal neurons. Brain Res 1998, 783, 77-84.
 
17.
Swinyard EA, Brown WC, Goodman LS: Comparative assays of antiepileptic drugs in mice and rats. J Pharmacol Exp Ther 1952, 106, 319-330.
 
18.
Wallace MJ, Blair RE, Faleński KW, Martin BR, DeLorenzo RJ: The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 2003, 307, 129-137.
 
19.
Wallace MJ, Martin BR, DeLorenzo RJ: Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol 2002, 452, 295-301.
 
20.
Wallace MJ, Wiley JL, Martin BR, DeLorenzo RJ: Assessment of the role of CB1 receptors in cannabinoid anticonvulsant eff ects. Eur J Pharmacol 2001, 428, 51-57.
 
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