RESEARCH PAPER
No effect of 7-nitroindazole on the anticonvulsant action of vigabatrin and oxcarbazepine in pentylenetetrazole-induced seizures in mice
| 1 | Department of Pathophysiology, Medical University, Lublin, Poland |
| 2 | Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland |
| 3 | First Department of Internal Medicine with Dialysis Station, County Hospital, Starachowice, Poland |
CORRESPONDING AUTHOR
Jarogniew J. Łuszczki
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2008;2(2):137–140
KEYWORDS
ABSTRACT
The aim of this study was to determine the effect of 7-nitroindazole (7-NI – a preferential neuronal nitric oxide synthase inhibitor) on the protective action of oxcarbazepine (OXC) and vigabatrin (VGB) – two newer antiepileptic drugs (AEDs) against pentylenetetrazole (PTZ)-induced seizures in mice. The clonic seizure activity in mice was evoked by subcutaneous injection of PTZ (100 mg/kg) and defined as clonus of the whole body lasting over 3 s with an accompanying loss of righting reflex in mice. The protective action of OXC and VGB against PTZ-induced clonic seizures was expressed as their median effective doses (ED50 values) suppressing clonic seizures in 50% of animals tested. The acute adverse-effect potentials of OXC and VGB in combination with 7-NI were evaluated in the chimney test (motor coordination) in mice. Results indicate that 7-NI administered intraperitoneally (50 mg/kg) did not significantly affect the anticonvulsant action of OXC or VGB against PTZ-induced clonic C. The ED50 values for OXC administered alone and in combination with 7-NI were 20.9 and 24.8 mg/kg. Similarly, the ED50 values for VGB administered alone and in combination with 7-NI were 595 and 622 mg/kg, respectively. Moreover, the examined combinations of 7-NI (50 mg/kg) with OXC (24.8 mg/kg) and VGB (622 mg/kg) did not aff ect motor coordination in the chimney test. In conclusion, 7-NI had no significant impact on the anticonvulsant activity of OXC and VGB in the mouse PTZ-induced seizure model, and did not affect motor coordination in animals subjected to the chimney test.
REFERENCES (29)
1.
Iadecola C: Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci 1997, 20, 132-139.
2.
Moncada S, Higgs EA: Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J 1995, 9, 1319-1330.
3.
Montecot C, Borredon J, Seylaz J, Pinard E: Nitric oxide of neuronal origin is involved in cerebral blood fl ow increase during seizures induced by kainate. J Cereb Blood Flow Metab 1997, 17, 94-99.
4.
Szabo C: Physiological and pathophysiological roles of nitric oxide in the central nervous system. Brain Res Bull 1996, 41, 131-141.
5.
Baran L, Siwanowicz J, Przegaliński E: Eff ect of nitric oxide synthase inhibitors and molsidomine on the anticonvulsant activity of some antiepileptic drugs. Pol J Pharmacol 1997, 49, 363-368.
6.
De Sarro G, Gareri P, Falconi U, De Sarro A: 7-Nitroindazole potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice. Eur J Pharmacol 2000, 394, 275-288.
7.
Łuszczki JJ, Czuczwar M, Gawlik P, Sawiniec-Poźniak G, Czuczwar K, Czuczwar SJ: 7-Nitroindazole potentiates the anticonvulsant action of some second-generation antiepileptic drugs in the mouse maximal electroshock-induced seizure model. J Neural Transm 2006, 113, 1157- 1168.
8.
Łuszczki JJ, Sacharuk A, Wojciechowska A, Andres MM, Dudra- Jastrzębska M, Mohamed M, Sawicka KM, Kozińska J, Czuczwar SJ: 7-Nitroindazole enhances dose-dependently the anticonvulsant activities of conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Pharmacol Rep 2006, 58, 660- 671.
9.
Smith SE, Man CM, Yip PK, Tang E, Chapman AG, Meldrum BS: Anticonvulsant eff ects of 7-nitroindazole in rodents with refl ex epilepsy may result from L-arginine accumulation or a reduction in nitric oxide or L-citrulline formation. Br J Pharmacol 1996, 119, 165-173.
10.
Tutka P, Łuszczki J, Kleinrok Z, Arent K, Wielosz M: Molsidomine enhances the protective activity of valproate against pentylenetetrazoleinduced seizures in mice. J Neural Transm 2002, 109, 455-466.
11.
Han D, Yamada K, Senzaki K, Xiong H, Nawa H, Nabeshima T: Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats. J Neurochem 2000, 74, 792-798.
12.
Borowicz KK, Łuszczki J, Kleinrok Z, Czuczwar SJ: 7-Nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazol-induced convulsions. J Neural Transm 2000, 107, 1117-1126
13.
Łuszczki JJ, Szadkowski M, Dudra-Jastrzębska M, Czernecki R, Filip D, Misiuta-Krzesińska M, Barcicka-Kłosowska B, Zwoliński J: 7- Nitroindazole does not aff ect the anti-convulsant action of gabapentin and tiagabine in pentylenetetrazole-induced seizures in mice. JPCCR 2007, 1, 150-154.
14.
Łuszczki JJ, Zadrożniak A, Barcicka-Kłosowska B, Bednarski J, Misiuta-Krzesińska M, Filip D, Zwoliński J, Czernecki R: Infl uence of 7-nitroindazole and NG-nitro-L-arginine on the anticonvulsant activity of loreclezole in maximal electroshock-induced seizures in mice. JPCCR 2007, 1, 146-149.
15.
Borowicz KK, Kleinrok Z, Czuczwar SJ: Infl uence of 7-nitroindazole on the anticonvulsive action of conventional antiepileptic drugs. Eur J Pharmacol 1997, 331, 127-132.
16.
Rajasekaran K, Jayakumar R, Venkatachalam K: Increased neuronal nitric oxide synthase (nNOS) activity triggers picrotoxin-induced seizures in rats and evidence for participation of nNOS mechanism in the action of antiepileptic drugs. Brain Res 2003, 979, 85-97.
17.
Loscher W, Honack D, Fassbender CP, Nolting B: The role of technical, biological and pharmacological factors in the laboratory evaluation anticonvulsant drugs. III. Pentylenetetrazole seizure models. Epilepsy Res 1991, 8, 171-189.
18.
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.
19.
Łuszczki JJ, Szadkowski M, Czuczwar SJ: Eff ect of NG-nitro-L-arginine on the anticonvulsive action of four second-generation antiepileptic drugs in pentetrazole-induced clonic seizures in mice. Pharmacol Rep 2007, 59, 467-473.
20.
Litchfi eld JT, Wilcoxon F: A simplifi ed method of evaluating dose-eff ect experiments. J Pharmacol Exp Ther 1949, 96, 99-113.
21.
Łuszczki JJ, Czuczwar SJ: Isobolographic profi le of interactions between tiagabine and gabapentin: a preclinical study. Naunyn Schmiedebergs Arch Pharmacol 2004, 369, 434-446.
22.
Łuszczki JJ, Czuczwar SJ: Isobolographic characterisation of interactions among selected newer antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model. Naunyn Schmiedebergs Arch Pharmacol 2005, 372, 41-54.
23.
Łuszczki JJ, Wojcik-Ćwikła J, Andres MM, Czuczwar SJ: Pharmacological and behavioral characteristics of interactions between vigabatrin and conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis. Neuropsychopharmacology 2005, 30, 958-973.
24.
Świąder M, Łuszczki J, Wielosz M, Czuczwar SJ: Infl uence of vigabatrin, a novel antiepileptic drug, on the anticonvulsant activity of conventional antiepileptics in pentetrazole-induced seizures in mice. Pol J Pharmacol 2003, 55, 363-370.
25.
Łuszczki JJ: Isobolographic analysis of interaction between oxcarbazepine and valproate in pentylenetetrazole-induced seizures in mice. JPCCR 2008, 2, 40-45.
26.
Boissier JR, Tardy J, Diverres JC: Une nouvelle methode simple pour explorer l’action ‘tranquilisante’: le test de la cheminee. Med Exp (Basel) 1960, 3, 81-84.
27.
Łuszczki JJ, Czuczwar M, Gawlik P, Sawiniec-Poźniak G, Czuczwar K, Sawicka KM, Dudra-Jastrzębska M, Czuczwar SJ: Infl uence of NGnitro- L-arginine on the anticonvulsant and acute adverse eff ects of some newer antiepileptic drugs in the maximal electroshock-induced seizures and chimney test in mice. Pharmacol Rep 2006, 58, 955-960.
28.
Czuczwar SJ, Tutka P, Klonowski P, Kleinrok Z: N(G)-nitro-Larginine impairs the anticonvulsive action of ethosuximide against pentylenetetrazol. Eur J Pharmacol 1999, 366, 137-142.
29.
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.
RELATED ARTICLE
The Journal of Pre-Clinical and Clinical Research welcomes article
submissions and does not charge a publication fee.
Submit your article today and gain worldwide visibility for your article.
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.