RESEARCH PAPER
Acute adverse-effect profi le of ethosuximide and stiripentol in the grip-strength test in mice
 
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Department of Pathophysiology, Medical University, Lublin, Poland; Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
CORRESPONDING AUTHOR
Jarogniew J. Łuszczki   

Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
 
J Pre Clin Clin Res. 2009;3(1):45–48
KEYWORDS
ABSTRACT
The aim of the study was assessment of acute adverse (neurotoxic) effects of ethosuximide and stiripentol (two antiepileptic drugs) in the grip-strength test by measuring skeletal muscular strength in mice. Linear regression analysis of dose-response relationship for drug doses and their corresponding skeletal muscular strength allowed determination of the doses of antiepileptic drugs that reduced the grip-strength in mice by 50%, compared with control animals. Results indicate that the experimentally-derived dose reducing muscular strength in mice by 50% (D50) for ethosuximide was 755.4 mg/kg and that for stiripentol was 971.2 mg/kg. The studied antiepileptic drugs reduced skeletal muscular strength in mice in a dose-dependent manner.
 
REFERENCES (26)
1.
MJ: Combination therapy in epilepsy: when and what to use. Drugs 2006, 66, 1817-1829.
 
2.
Kwan P, Brodie MJ: Refractory epilepsy: a progressive, intractable but preventable condition? Seizure 2002, 11, 77-84.
 
3.
Brodie MJ, Schachter SC: Fast Facts. Epilepsy, 2nd edn., Health Press, Oxford, 2001.
 
4.
Deckers CL, Czuczwar SJ, Hekster YA, Keyser A, Kubova H, Meinardi H, Patsalos PN, Renier WO, Van Rijn CM: Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed. Epilepsia 2000, 41, 1364-1374.
 
5.
Perucca E, Kwan P: Overtreatment in epilepsy: how it occurs and how it can be avoided. CNS Drugs 2005, 19, 897-908.
 
6.
Perucca E: Pharmacological principles as a basis for polytherapy. Acta Neurol Scand Suppl 1995, 162, 31-34.
 
7.
Schmidt D: Strategies to prevent overtreatment with antiepileptic drugs in patients with epilepsy. Epilepsy Res 2002, 52, 61-69.
 
8.
Loscher W, Nolting B: The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. IV. Protective indices. Epilepsy Res 1991, 9, 1-10.
 
9.
Łuszczki JJ, Zadrożniak A, Wlaź A, Andres-Mach M, Dudra-Jastrzębska M, Zwoliński J, Misiuta-Krzesińska M, Sielski M: Characterization of acute adverse-eff ect profi le of carbamazepine and valproate in the grip-strength test in mice. J Pre-Clin Clin Res 2008, 2, 46-48.
 
10.
Zadrożniak A, Wojda E, Wlaź A, Łuszczki JJ: Characterization of acute adverse-eff ect profi le of some selected antiepileptic drugs in the grip-strength test in mice. Pharmacol Rep 2009, 61, In press.
 
11.
Motulsky HJ, Christopoulos A: Fitting models to biological data using linear and nonlinear regression. A practical guide to curve fi tting. GraphPad Software Inc., San Diego CA, 2003.
 
12.
Łuszczki JJ, Andres MM, Czuczwar P, Cioczek-Czuczwar A, WojcikĆwikła J, Ratnaraj N, Patsalos PN, Czuczwar SJ: Levetiracetam selectively potentiates the acute neurotoxic eff ects of topiramate and carbamazepine in the rotarod test in mice. Eur Neuropsychopharmacol 2005, 15, 609-616.
 
13.
Łuszczki JJ, Andres MM, Czuczwar P, Cioczek-Czuczwar A, WojcikĆwikła J, Ratnaraj N, Patsalos PN, Czuczwar SJ: Levetiracetam selectively potentiates the acute neurotoxic eff ects of topiramate and carbamazepine in the rotarod test in mice. Eur Neuropsychopharmacol 2005, 15, 609-617.
 
14.
Łuszczki JJ, Czuczwar M, Kiś J, Krysa J, Pasztelan I, Świąder M, Czuczwar SJ: Interactions of lamotrigine with topiramate and fi rstgeneration antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis. Epilepsia 2003, 44, 1003-1013.
 
15.
Meyer OA, Tilson HA, Byrd WC, Riley MT: A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehav Toxicol 1979, 1, 233-236.
 
16.
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.
 
17.
Coulter DA, Huguenard JR, Prince DA: Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol 1998, 25, 582-593.
 
18.
Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E: Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol 2001, 60, 1121-1132.
 
19.
Leresche N, Parri HR, Erdemli G, Guyon A, Turner JP, Williams SR, Asprodini E, Crunelli V: On the action of the antiabsence drug ethosuximide in the rat and cat thalamus. J Neurosci 1998, 18, 4842- 4853.
 
20.
Crunelli V, Leresche N: Block of thalamic T-type Ca2+ channels by ethosuximide is not the whole story. Epilepsy Curr 2002, 2, 53-56.
 
21.
Kobayashi T, Hirai H, Iino M, Fuse I, Mitsumura K, Washiyama K, Kasai S, Ikeda K: Inhibitory eff ects of the antiepileptic drug ethosuximide on G protein-activated inwardly rectifying K+ channels. Neuropharmacology 2009, 56, 499-506.
 
22.
Poisson M, Huguet F, Savattier A, Bakri-Logeais F, Narcisse G: A new type of anticonvulsant, stiripentol. Pharmacological profi le and neurochemical study. Arzneimittelforschung 1984, 34, 199-204.
 
23.
Wegmann R, Ilies A, Aurousseau M: Pharmaco-cellular enzymology of the mechanism of action of stiripentol in cardiazol-induced epilepsy. III. Protein, nucleoprotein, lipid, and proteoglycan metabolism. Cell Mol Biol Incl Cyto-Enzymol 1978, 23, 455-480.
 
24.
Quilichini PP, Chiron C, Ben-Ari Y, Gozlan H: Stiripentol, a putative antiepileptic drug, enhances the duration of opening of GABA receptor channels. Epilepsia 2006, 47, 704-716.
 
25.
Shen DD, Levy RH, Savitch JL, Boddy AV, Tombret F, Lepage F: Comparative anticonvulsant potency and pharmacokinetics of (+)- and (-)-enantiomers of stiripentol. Epilepsy Res 1992, 12, 29-36.
 
26.
Than M, Kocsis P, Tihanyi K, Fodor L, Farkas B, Kovacs G, Kis-Varga A, Szombathelyi Z, Tarnawa I: Concerted action of antiepileptic and antidepressant agents to depress spinal neurotransmission: Possible use in the therapy of spasticity and chronic pain. Neurochem Int 2007, 50, 642-652.
 
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