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1

Experimental background for the search of new antiepileptic drugs

100%
Czuczwar S. J.
Acta Neurobiologiae Experimentalis
|
1999
|
tom 59
|
nr 3
2
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Effect of topiramate and its combination with SIB-1893 on body temperature in rats

51%
Luszczki J. J., Ossowska G., Czuczwar S. J.
Journal of Pre-Clinical and Clinical Research
|
2009
|
tom 03
|
nr 2
3
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Assessment of combined treatment with vigabatrin and antihypertensive drugs against electroconvulsions in mice

51%
Lukawski K., Raszewski G., Czuczwar S. J.
Journal of Pre-Clinical and Clinical Research
|
2015
|
tom 09
|
nr 1
Introduction and objective: It is likely that cardiovascular drugs will be used in epileptic patients because heart failure and hypertension are common comorbid conditions with epilepsy. Experimental studies show that some cardiovascular drugs can affect the protective activity of antiepileptics. The aim of this study was to examine the effects in mice of angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril), angiotensin AT1 receptor antagonists (losartan and candesartan) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of vigabatrin (VGB), a second generation antiepileptic drug. Material and Methods: Adult Swiss mice were used in the study. The anticonvulsant action of VGB was assessed in the maximal electroshock seizure threshold test. Combined treatment with VGB and antihypertensive drugs was also tested for adverse effects in the passive avoidance task and chimney test. All drugs were administered intraperitoneally. Results: Captopril (50 mg/kg), perindopril (10 mg/kg), losartan (50 mg/kg), candesartan (8 mg/kg), hydrochlorothiazide (100 mg/kg) and ethacrynic acid (100 mg/kg) did not influence the protective action of VGB. The combined treatment with VGB (700 mg/kg) and antihypertensive drugs showed a strong tendency towards impaired retention in the passive avoidance task, and in the case of the combination of VGB with ethacrynic acid it reached statistical significance (P < 0.05). Mice were not disturbed in the chimney test following applied treatment. Conclusions: From the preclinical point of view, the use of the tested antihypertensive drugs in patients treated with VGB seems neutral regarding its anticonvulsant activity.
4
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Influence of oxcarbazepine and its combination with SIB-1893 on body temperature in rats

51%
Luszczycki J. J., Borowicz K. K., Czuczwar S. J.
Journal of Pre-Clinical and Clinical Research
|
2008
|
tom 02
|
nr 1
5

Influence of LY 300164 (a novel non-NMDA antagonist) on the anticonvulsive activity of antieplleptics

51%
Czuczwar S. J., Swiader M., Kuzniar H., Kleinrok Z.
Acta Neurobiologiae Experimentalis
|
1997
|
tom 57
|
nr 5
6
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Evaluation of the combined treatment with pregabalin and inhibitors of the renin-angiotensin system against maximal electroshock in mice

51%
Lukawski K., Raszewski G., Czuczwar S. J.
Journal of Pre-Clinical and Clinical Research
|
2018
|
tom 12
|
nr 2
7

Riluzole, an inhibitor of glutamate release, potentiates the protective activity of conventional antiepileptic drugs against electroconwlsions in mice

51%
Czuczwar S. J., Klenk-Majewska B., Szymczyk G.
Acta Neurobiologiae Experimentalis
|
1997
|
tom 57
|
nr 5
8

Excitatory amino acids, antiepileptic drugs, and seizure activity

51%
Czuczwar S. J., Turski W. A., Kleinrok Z.
Acta Neurobiologiae Experimentalis
|
1995
|
tom 55
|
nr 5
9

Interaction of excitatory amino acid antagonists and calcium channel inhibitors in the electroconvulsive test in mice

51%
Gasior M., Borowicz K. K., Kleinrok Z., Czuczwar S. J.
Acta Neurobiologiae Experimentalis
|
1995
|
tom 55
|
nr 5
10

7-nitroindazole (a selective neuronal nitric oxide synthase inhibitor) differentially affects the anticonvczsive activity of conventional antiepileptics in mice

51%
Czuczwar S. J., Borowicz K. K., Kleinrok Z.
Acta Neurobiologiae Experimentalis
|
1997
|
tom 57
|
nr 5
11
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Effects of fluoxetine on the anticonvulsant action of valproate and ethosuximide in mouse model of myoclonic convulsions

51%
Borowicz K. K., Piskorska B., Stepniak B., Czuczwar S. J.
Annals of Agricultural and Environmental Medicine
|
2012
|
tom 19
|
nr 3
Depression is becoming a growing problem in rural areas. This psychiatric disorder often accompanies epilepsy. The aim of this study was to assess the influence of fluoxetine (FXT), a commonly used antidepressant, on the protective action of two conventional antiepileptic drugs: ethosuximide (ETX) and valproate (VPA), against pentylenetetrazole (PTZ)-induced convulsions in mice. Motor coordination and long-term memory deficits induced by FXT, antiepileptic drugs alone and in combinations with FXT were assessed in the chimney test and passive-avoidance task, respectively. Brain concentrations of ETX and VPA were measured by immunofluorescence. Obtained results indicate that FXT at the dose of 15 mg/kg (ip, 30 min before the test) significantly increased the threshold for clonic convulsions. The antidepressant drug at lower doses remained ineffective in this respect. Moreover, FXT at the highest subprotective dose (10 mg/kg, ip) markedly enhanced the anticonvulsant effects of VPA, but not of ETX, against PTZ-induced seizures. The interaction between FXT and VPA seems to be pharmacodynamic because the antidepressant drug did not alter the brain concentration of VPA. With regard to adverse effects, FXT, VPA, ETX, and the combinations of FXT with antiepileptic drugs, did not impair motor coordination and long-term memory in mice. In conclusion, the combination of FXT with VPA may be advantageous in the treatment of myoclonic epilepsy, and therefore it should be recommended for further study in clinical conditions.
12

Excitatory amino acid neurotransmission and the anticonvulsive activity of antiepileptic drugs

51%
Czuczwar S. J., Kleinrok Z., Turski W. A.
Acta Neurobiologiae Experimentalis
|
1997
|
tom 57
|
nr 5
13

CGP 40116, a competitive antagonist of NMDA receptors, and the protective potency of common antiepileptic drugs against maximal electroshock

51%
Czuczwar S. J., Hussein Q., Kleinrok Z.
Acta Neurobiologiae Experimentalis
|
1997
|
tom 57
|
nr 5
14
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Neuroprotective effects of some newer and potential antiepileptic drugs

51%
Czuczwar S. J., Ferenc R., Blaszczyk B., Borowicz K. K.
Journal of Pre-Clinical and Clinical Research
|
2007
|
tom 01
|
nr 1
15

Anticonvulsant effects of selected antiepileptic drugs in mice exposed to caffeine during pregnancy and breastfeeding in the maximal electroshock-induced seizure model

51%
Miziak B., Radzik I., Czuczwar S. J.
Acta Neurobiologiae Experimentalis
|
2017
|
tom 77
|
nr Suppl.1
INTRODUCTION: Caffeine presence in coffee, tea and some drugs makes it the most commonly consumed stimulant drug. Available data show that consumption of caffeine during pregnancy and in the early postpartum period while breastfeeding can affect the offspring’s behaviour at the later stages of life. AIM(S): The aim was to test the impact of caffeine fed to pregnant and breastfeeding mice on the anticonvulsant activity of selected antiepileptic drugs (AEDs): sodium valproate (VPA), topiramate (TPM) and carbamazepine (CBZ), against the maximal electroshock-induced seizures (MES). METHOD(S): From the 3 day after fertilization, pregnant mice received caffeine dissolved in drinking water throughout the pregnancy, and then throughout breastfeeding. The experiments were carried out on adult offspring (mice in their 8th week of age). The control groups comprised mice, born by females that received only pure water throughout the pregnancy and then throughout breastfeeding while experimental groups – mice, born by females that drank caffeine (0.3 g/l). Seizures were induced by alternating current (25 mA, 50 Hz, stimulus duration 0.2 s) delivered by a generator via ear electrodes. Undesirable effects of the combined treatments were examined in the chimney test, passive avoidance task, and grip strength test. RESULTS: In the groups exposed to caffeine, there was a significant impairment of the anticonvulsant action of both, VPA and CBZ. The respective ED50s were increased from 155.5 (146.2–165.4) to 175.5 (164.1–187.7) and from 8.4 (6.9–10.3) to 11.6 (10.5–12.9) mg/kg, respectively. As regards TPM, no significant impact of exposure to caffeine on the effectiveness of this AED has been observed. The neurotoxic effects of AEDs were not affected by caffeine exposure. CONCLUSIONS: The experiments show that exposure to caffeine has a statistically relevant influence on the anticonvulsant action of VPA and CBZ against MES test carried out in the exposed offspring. FINANCIAL SUPPORT: DS 475.
16
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Interaction between diuretics and tiagabine in the maximal electroshock seizure threshold test in mice

51%
Lukawski K., Swiderska G., Czuczwar S. J.
Journal of Pre-Clinical and Clinical Research
|
2010
|
tom 04
|
nr 1
17
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Neurotoxic effects of combined exposure to caffeine and pyrethroids in mice

51%
Lukawski K., Raszewski G., Czuczwar S. J.
Annals of Agricultural and Environmental Medicine
|
2022
|
tom 29
|
nr 3
18
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Clinical considerations on the relationship between epilepsy and cardiovascular diseases

45%
Trojnar M. P., Kimber-Trojnar Z., Trojnar M. K., Luszczki J. J., Czuczwar S. J.
Journal of Pre-Clinical and Clinical Research
|
2007
|
tom 01
|
nr 1
19
Content available remote

Influence of several convulsants on the protective activity of a non-competitive AMPA-kainate antagonist, LY 300164, and lamotrigine against maximal electroshock in mice

39%
Borowicz K. K., Swiader M., Zgrajka W., Sawulski C., Turski W. A., Czuczwar S. J.
Journal of Physiology and Pharmacology
|
2002
|
tom 53
|
nr 4,2
Aminophylline (50-100 mg/kg) and strychnine (0.125-0.5 mg/kg) significantly raised the ED50 values of LY 300164 against maximal electroshock in mice, from 4 to 8 mg/kg (aminophylline 100 mg/kg) and from 3.6 to 11.5 mg/kg (strychnine 0.5 mg/kg). Also, aminophylline (25-50 mg/kg) and strychnine (0.125-0.25 mg/kg) increased the ED50 value of lamotrigine in this test, for instance from 5.5 to 8.0 mg/kg (aminophylline 50 mg/kg) and from 5.2 to 8.9 mg/kg (strychnine 0.25 mg/kg). Moreover, the ED50s values of aminophylline and strychnine for the reduction of the anticonvulsant effect of LY 300164 (7 mg/kg, the dose equal to its ED97 value against maximal electroshock) were 79.9 and 0.2 mg/kg, respectively. The respective ED50 values for the inhibition of the antiseizure action of lamotrigine were 40.9 and 0.2 mg/kg. Neither bicuculline nor picrotoxin affected the protective action of LY 300164 or lamotrigine. Strychnine significantly lowered the plasma concentrations of LY 300164 and this my point to a pharmacokinetic mechanism of the observed interaction. Aminophylline did not affect the plasma concentrations of the studied anticonvulsant drugs and strychnine - that of lamotrigine, so a pharmacokinetic interaction does not seem probable. The present results indicate that the potential of aminophylline and strychnine to attenuate the anticonvulsant activity of conventional antiepileptics is extended to LY 300164 and lamotrigine.
20
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Isobolographic assessment of interactions between retigabine and phenytoin in the mouse maximal electroshock-induced seizure model and chimney test

27%
Zolkowska D., Zagaja M., Miziak B., Kondrat-Wrobel M. W., Zaluska K., Florek-Luszczki M., Szpringer M., Drop B., Zadrozniak M., Czuczwar S. J., Luszczki J. J.
Health Problems of Civilization
|
2016
|
tom 10
|
nr 4
Background. Search for beneficial combinations of antiepileptic drugs (AEDs) that can be used in patients with pharmacoresistant epilepsy, is still conducted both empirically and rationally, based on molecular mechanisms of AEDs’ action. This study was aimed at characterizing the interaction profiles for the combination of two AEDs (i.e., retigabine [RTG] and phenytoin [PHT]) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male albino Swiss mice. Material and methods. Type I isobolographic analysis was used to determine interactions for the combination of RTG with PHT (at three fixed-ratios of 1:3, 1:1 and 3:1) with respect to its anticonvulsant and acute neurotoxic effects in the MES and chimney tests, respectively. Total brain concentrations of RTG and PHT were estimated to exclude any pharmacokinetic interaction between AEDs. Results. The combination of RTG with PHT at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in both, the MES and chimney tests. RTG and PHT did not affect each other their total brain concentrations in mice, confirming pharmacodynamic interaction between the investigated drugs. Conclusions. The combination of RTG with PHT was neutral suggesting that this two-drug combination might occur favorable in some patients with refractory epilepsy.
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