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Stanisław J. Czuczwar - One of the best experts on this subject based on the ideXlab platform.

  • Interactions between ACE inhibitors and classical antiepileptic drugs in the mouse Maximal Electroshock Seizures
    Pharmacology Biochemistry and Behavior, 2011
    Co-Authors: Krzysztof Łukawski, Tomasz Jakubus, Agnieszka Janowska, Stanisław J. Czuczwar
    Abstract:

    Abstract This study evaluated the effect of two angiotensin-converting enzyme (ACE) inhibitors, enalapril and cilazapril, commonly used antihypertensive drugs, on the protective efficacy of the classical antiepileptics — carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and phenobarbital (PB). For this purpose, we used the Maximal Electroshock Seizure (MES) test in mice. Additionally, adverse effects of combined treatment with ACE inhibitors and antiepileptic drugs in the passive avoidance task and chimney test were assessed. All drugs were administered intraperitoneally. Neither enalapril (10, 20 and 30 mg/kg) nor cilazapril (5, 10 and 20 mg/kg) affected the threshold for electroconvulsions. Enalapril (30 mg/kg) but not cilazapril (20 mg/kg), enhanced the protective action of VPA, decreasing its ED50 value from 249.5 to 164.9 mg/kg (p

  • Captopril potentiates the anticonvulsant activity of carbamazepine and lamotrigine in the mouse Maximal Electroshock Seizure model
    Journal of Neural Transmission, 2010
    Co-Authors: Krzysztof Łukawski, Tomasz Jakubus, Grzegorz Raszewski, Stanisław J. Czuczwar
    Abstract:

    Some studies suggest a higher risk of hypertension in people with epilepsy. Captopril, a potent and selective angiotensin-converting enzyme (ACE) inhibitor, is a well known antihypertensive drug. Besides the peripheral renin–angiotensin system (RAS), ACE inhibitors are also suggested to affect the brain RAS which might participate in the regulation of Seizure susceptibility. The purpose of the current study was to evaluate the effect of captopril on the protective action of numerous antiepileptic drugs (carbamazepine [CBZ], phenytoin [PHT], valproate [VPA], phenobarbital [PB], oxcarbazepine [OXC], lamotrigine [LTG] and topiramate [TPM]) against Maximal Electroshock-induced Seizures in mice. This study was accompanied by an evaluation of adverse effects of combined treatment with captopril and antiepileptic drugs in the passive avoidance task and chimney test. Captopril (25 and 50 mg/kg i.p.) did not influence the threshold for electroconvulsions. Among the tested antiepileptics, captopril (25 and 50 mg/kg i.p.) potentiated the antiSeizure action of CBZ, decreasing its ED_50 value from 12.1 to 8.9 and 8.7 mg/kg, respectively. Moreover, captopril (50 mg/kg i.p.) enhanced the anticonvulsant activity of LTG. ED_50 value for LTG was lowered from 5.1 to 3.5 mg/kg. The observed interactions between captopril and CBZ or LTG were pharmacodynamic in nature as captopril did not alter plasma and total brain concentrations of these antiepileptics. The combinations of captopril with antiepileptic drugs did not lead to retention deficits in the passive avoidance task or motor impairment in the chimney test. Based on the current preclinical data, it is suggested that captopril may positively interact with CBZ and LTG in epileptic patients. The combinations of captopril with the remaining antiepileptics (PHT, VPA, PB, OXC and TPM) seem neutral.

  • Influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse Maximal Electroshock Seizure model
    Pharmacological Reports, 2010
    Co-Authors: Krzysztof Łukawski, Grażyna Świderska, Jarogniew J. Łuszczki, Stanisław J. Czuczwar
    Abstract:

    The aim of this study was to determine whether ethacrynic acid (EA), a loop diuretic with anticonvulsant activity, would affect the protective action of the conventional antiepileptics (AEDs) carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and phenobarbital (PB) in the mouse Maximal Electroshock Seizure (MES) model. The effects of acute and chronic treatment with EA on these AEDs were examined. At a single dose of 100 mg/kg ip , EA enhanced the antiElectroshock activity of VPA, decreasing its ED50 value from 225.6 to 146.6 mg/kg (p < 0.05), but enhancement was not observed following continuous administration of EA (12.5 mg/kg) for seven days. Combined treatment of EA with other AEDs had no effect on their ED_50 values. The observed interaction between EA and VPA was pharmacodynamic in nature as EA did not alter free plasma (non-protein-bound) and total brain concentrations of VPA. Taking into consideration the clinical use of both drugs, this interaction between EA and VPA can be important for patients receiving these drugs.

  • Interaction between diuretics and tiagabine in the Maximal Electroshock Seizure threshold test in mice
    Journal of Pre-Clinical and Clinical Research, 2010
    Co-Authors: Krzysztof Łukawski, Grażyna Świderska, Stanisław J. Czuczwar
    Abstract:

    It has been reported that loop diuretics can aff ect the antiSeizure action of valproate (VPA) and topiramate (TPM) in mice. This study evaluated the eff ect of ethacrynic acid (EA), a loop diuretic, and hydrochlorothiazide (HCTZ), a thiazide-type diuretic, on the anticonvulsant activity of tiagabine (TGB), a newer antiepileptic drug, in the Maximal Electroshock Seizure threshold test. The threshold for electroconvulsions is regarded as an experimental model of tonic-clonic Seizures in humans. Diuretics were administered intraperitoneally (i.p.) at single doses (acute treatment) or once daily for seven days (chronic administration). EA at subthreshold doses of 12.5 mg/kg (chronic) and 100 mg/kg (acute) did not aff ect the anticonvulsant activity of TGB. Similarly, HCTZ at the subthreshold dose of 100 mg/kg, both in acute and chronic experiments, remained without eff ect on the anticonvulsant action of TGB. From the preclinical point of view, the use of tested diuretics in epileptic patients receiving TGB is presumed neutral upon its anticonvulsant potency.

  • effect of arachidonyl 2 chloroethylamide a selective cannabinoid cb1 receptor agonist on the protective action of the various antiepileptic drugs in the mouse Maximal Electroshock induced Seizure model
    Progress in Neuro-psychopharmacology & Biological Psychiatry, 2010
    Co-Authors: Jarogniew J Luszczki, Monika Dudrajastrzebska, Marta Andresmach, Piotr Czuczwar, Anna Cioczekczuczwar, Stanisław J. Czuczwar
    Abstract:

    Abstract The aim of this study was to determine the influence of arachidonyl-2′-chloroethylamide (ACEA — a highly selective cannabinoid type 1 [CB1] receptor agonist) on the protective action and acute adverse effects of carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, and topiramate in the Maximal Electroshock Seizure model and chimney test in mice. Tonic hind limb extension (Seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the studied antiepileptic drugs with respect to motor coordination was assessed in the chimney test. Additionally, long-term memory and skeletal muscular strength were measured along with free plasma (non-protein bound) and total brain antiepileptic drug concentrations. To inhibit the rapid metabolic degradation of ACEA by the fatty-acid amide hydrolase, phenylmethylsulfonyl fluoride (PMSF) was used at a constant ineffective dose of 30 mg/kg. Results indicate that ACEA (2.5 mg/kg, i.p.) co-administered with PMSF (30 mg/kg, i.p.), significantly enhanced the anticonvulsant activity of phenobarbital, but not that of carbamazepine, lamotrigine, oxcarbazepine, phenytoin, or topiramate in the Maximal Electroshock Seizure test in mice. Moreover, ACEA (2.5 mg/kg) with PMSF (30 mg/kg) had no significant impact on the acute adverse effects of all examined antiepileptic drugs in the chimney test in mice. The protective index values (as quotients of the respective TD 50 and ED 50 values denoted from the chimney and Maximal Electroshock Seizure tests, respectively) for the combinations of ACEA (2.5 mg/kg) and PMSF (30 mg/kg) with carbamazepine, oxcarbazepine, phenobarbital, and topiramate were greater than those denoted for the antiepileptic drugs administered alone. Only, the protective index values for the combination of ACEA (2.5 mg/kg) and PMSF (30 mg/kg) with lamotrigine and phenytoin were lower than those determined for the antiepileptic drugs administered alone. Pharmacokinetic experiments revealed that ACEA (2.5 mg/kg) and PMSF (30 mg/kg) affected neither free plasma (non-protein bound) nor total brain concentrations of phenobarbital in mice. Moreover, ACEA and PMSF in combination with carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, and topiramate did not alter long-term memory or skeletal muscular strength in experimental animals. In conclusion, the enhanced anticonvulsant action of phenobarbital by ACEA and PMSF, lack of pharmacokinetic interaction and no acute adverse effects between the examined compounds, make the combination of ACEA and PMSF with phenobarbital of pivotal importance for further experimental and clinical studies. The combinations of ACEA and PMSF with carbamazepine, lamotrigine, oxcarbazepine, phenytoin, and topiramate are neutral from a preclinical viewpoint.

Jarogniew J Luszczki - One of the best experts on this subject based on the ideXlab platform.

  • effect of arachidonyl 2 chloroethylamide a selective cannabinoid cb1 receptor agonist on the protective action of the various antiepileptic drugs in the mouse Maximal Electroshock induced Seizure model
    Progress in Neuro-psychopharmacology & Biological Psychiatry, 2010
    Co-Authors: Jarogniew J Luszczki, Monika Dudrajastrzebska, Marta Andresmach, Piotr Czuczwar, Anna Cioczekczuczwar, Stanisław J. Czuczwar
    Abstract:

    Abstract The aim of this study was to determine the influence of arachidonyl-2′-chloroethylamide (ACEA — a highly selective cannabinoid type 1 [CB1] receptor agonist) on the protective action and acute adverse effects of carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, and topiramate in the Maximal Electroshock Seizure model and chimney test in mice. Tonic hind limb extension (Seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the studied antiepileptic drugs with respect to motor coordination was assessed in the chimney test. Additionally, long-term memory and skeletal muscular strength were measured along with free plasma (non-protein bound) and total brain antiepileptic drug concentrations. To inhibit the rapid metabolic degradation of ACEA by the fatty-acid amide hydrolase, phenylmethylsulfonyl fluoride (PMSF) was used at a constant ineffective dose of 30 mg/kg. Results indicate that ACEA (2.5 mg/kg, i.p.) co-administered with PMSF (30 mg/kg, i.p.), significantly enhanced the anticonvulsant activity of phenobarbital, but not that of carbamazepine, lamotrigine, oxcarbazepine, phenytoin, or topiramate in the Maximal Electroshock Seizure test in mice. Moreover, ACEA (2.5 mg/kg) with PMSF (30 mg/kg) had no significant impact on the acute adverse effects of all examined antiepileptic drugs in the chimney test in mice. The protective index values (as quotients of the respective TD 50 and ED 50 values denoted from the chimney and Maximal Electroshock Seizure tests, respectively) for the combinations of ACEA (2.5 mg/kg) and PMSF (30 mg/kg) with carbamazepine, oxcarbazepine, phenobarbital, and topiramate were greater than those denoted for the antiepileptic drugs administered alone. Only, the protective index values for the combination of ACEA (2.5 mg/kg) and PMSF (30 mg/kg) with lamotrigine and phenytoin were lower than those determined for the antiepileptic drugs administered alone. Pharmacokinetic experiments revealed that ACEA (2.5 mg/kg) and PMSF (30 mg/kg) affected neither free plasma (non-protein bound) nor total brain concentrations of phenobarbital in mice. Moreover, ACEA and PMSF in combination with carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, and topiramate did not alter long-term memory or skeletal muscular strength in experimental animals. In conclusion, the enhanced anticonvulsant action of phenobarbital by ACEA and PMSF, lack of pharmacokinetic interaction and no acute adverse effects between the examined compounds, make the combination of ACEA and PMSF with phenobarbital of pivotal importance for further experimental and clinical studies. The combinations of ACEA and PMSF with carbamazepine, lamotrigine, oxcarbazepine, phenytoin, and topiramate are neutral from a preclinical viewpoint.

  • Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the Maximal Electroshock Seizure and chimney tests in mice: a comparative study.
    Epilepsy research, 2009
    Co-Authors: Jarogniew J Luszczki, Ewa Wojda, Marta Andres-mach, Wojciech Cisowski, Michal Glensk, Kazimierz Glowniak, Stanisław J. Czuczwar
    Abstract:

    The aim of this study was to determine and compare the anticonvulsant and acute adverse (neurotoxic) effects of imperatorin and osthole (two natural coumarin derivatives) with valproate (a classical antiepileptic drug) in the Maximal Electroshock Seizure and chimney tests in mice. The anticonvulsant and acute adverse effects of imperatorin, osthole and valproate were determined at 15, 30, 60 and 120 min after their systemic (i.p.) administration. The evaluation of time-course and dose-response relationships for imperatorin, osthole and valproate in the Maximal Electroshock Seizure test revealed that the compounds produced a clear-cut antiElectroshock action in mice and the experimentally derived ED(50) values for imperatorin ranged between 167 and 290 mg/kg, those for osthole ranged from 253 to 639 mg/kg, whereas the ED(50) values for valproate ranged from 189 to 255 mg/kg. The evaluation of acute neurotoxic effects in the chimney test revealed that the TD(50) values for imperatorin ranged between 329 and 443 mg/kg, the TD(50) values for osthole ranged from 531 to 648 mg/kg, while the TD(50) values for valproate ranged from 363 to 512 mg/kg. The protective index (as a ratio of TD(50) and ED(50) values) for imperatorin ranged between 1.13 and 2.60, for osthole ranged from 0.83 to 2.44, and for valproate ranged between 1.72 and 2.00. In conclusion, both natural coumarin derivatives deserve more attention from a preclinical point of view as compounds possessing some potentially favorable activities in terms of suppression of Seizures, quite similar to those reported for valproate.

  • N-(anilinomethyl)-p-isopropoxyphenylsuccinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse Maximal Electroshock-induced Seizure model.
    Neuroscience Research, 2009
    Co-Authors: Jarogniew J Luszczki, Sergey L. Kocharov, Stanisław J. Czuczwar
    Abstract:

    The aim of this study was to determine the influence of N-(anilinomethyl)-p-isopropoxyphenylsuccinimide (AMIPPS) on the protective action of carbamazepine, phenobarbital, phenytoin, and valproate in the mouse Maximal Electroshock Seizure model. Results indicate that AMIPPS administered separately (i.p., at doses of 75 and 150 mg/kg), significantly elevated the threshold for electroconvulsions in mice. Moreover, AMIPPS (37.5 mg/kg) significantly enhanced the anticonvulsant activity of phenobarbital and valproate, but not that of carbamazepine or phenytoin in the Maximal Electroshock Seizure test in mice. AMIPPS (18.75 mg/kg) had no impact on the antiSeizure action of phenobarbital and valproate against Maximal Electroshock Seizure-induced Seizures in mice. Pharmacokinetic experiments revealed that AMIPPS significantly increased total brain valproate concentrations and it had no impact on total brain concentrations of phenobarbital in mice. In conclusion, the enhanced antiElectroshock action of phenobarbital by AMIPPS and lack of pharmacokinetic interaction make the combination of AMIPPS with phenobarbital of pivotal importance for further experimental and clinical studies. Although AMIPPS potentiated the anticonvulsant action of valproate in the Maximal Electroshock Seizure test, the caution is advised when combining these drugs due to the risk of pharmacokinetic interactions. The combinations of AMIPPS with carbamazepine and phenytoin are neutral from a preclinical viewpoint.

  • Osthole suppresses Seizures in the mouse Maximal Electroshock Seizure model.
    European journal of pharmacology, 2009
    Co-Authors: Jarogniew J Luszczki, Marta Andres-mach, Wojciech Cisowski, Kazimierz Glowniak, Irena Mazol, Stanislaw J Czuczwar
    Abstract:

    The aim of this study was to determine the anticonvulsant effects of osthole {[7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one]--a natural coumarin derivative} in the mouse Maximal Electroshock-induced Seizure model. The antiSeizure effects of osthole were determined at 15, 30, 60, and 120 min after its systemic (i.p.) administration. Time course of anticonvulsant action of osthole revealed that the natural coumarin derivative produced a clear-cut antiElectroshock activity in mice and the experimentally-derived ED(50) values for osthole ranged from 259 to 631 mg/kg. In conclusion, osthole suppresses Seizure activity in the mouse Maximal Electroshock-induced Seizure model. It may become a novel treatment option following further investigation in other animal models of epilepsy and preclinical studies.

  • Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against Maximal Electroshock-induced Seizures in mice
    Advances in Medical Sciences, 2009
    Co-Authors: Justyna Kozińska, Katarzyna M. Sawicka, Ewa Wojda, Marta Andres-mach, Anna Zadrożniak, Monika Dudra-jastrzębska, Jarogniew J Luszczki
    Abstract:

    Purpose: To determine the influence of indapamide on the protective action of numerous conventional and second-generation antiepileptic drugs (carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, topiramate and valproate) in the mouse Maximal Electroshock Seizure model. Material and Methods: Electroconvulsions were evoked in Albino Swiss mice by a current (sine-wave, 0.2 s stimulus duration) delivered via auricular electrodes. Adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. Results: Indapamide (up to 3 mg/kg, i.p., 120 min before the test) neither altered the threshold for Maximal electroconvulsions, nor protected the animals against Maximal Electroshock-induced Seizures in mice. Moreover, indapamide (3 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenobarbital and valproate, but not that of lamotrigine, oxcarbazepine or topiramate in the Maximal Electroshock Seizure test in mice. Indapamide (1.5 mg/kg) had no impact on the anticonvulsant action of all studied antiepileptic drugs in the Maximal Electroshock Seizure test in mice. Estimation of total brain antiepileptic drug concentrations revealed that the observed interaction between indapamide and phenobarbital was complicated by a significant pharmacokinetic increase in total brain concentrations of phenobarbital. In contrast, indapamide had no impact on the total brain concentrations of carbamazepine and valproate in mice. Conclusions: The selective potentiation of the anticonvulsant action of carbamazepine and valproate by indapamide and lack of any pharmacokinetic interactions between drugs, make the combinations of indapamide with carbamazepine or valproate of pivotal importance for epileptic patients taking these drugs together.

Waquar Ahsan - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis of new piperidyl indanone derivatives as anticonvulsant agents
    Medicinal Chemistry Research, 2012
    Co-Authors: Nadeem Siddiqui, S A Khan, Waquar Ahsan, M. Faiz Arshad, Ruhi Ali, M. Shamsher Alam, Sharique Ahmed
    Abstract:

    A series of 5,6-dimethoxy-2-{1-[arylamino/alkylamino(thioxo)methyl]-4-piperidyl-methyl}-1-indanones ( 4a – l ) were designed and synthesized by the reaction of 5,6-dimethoxy-2-(piperidin-4-yl-methyl)-indan-1-one with aryl/alkyl isothiocyanates. The anticonvulsant activity was evaluated in animal models by Maximal Electroshock Seizure and subcutaneous pentylenetetrazole tests. The neurotoxic effects were assessed by rotorod and ethanol potentiation tests. Gamma amino butyric acid (GABA) estimation of the selected compounds was performed in rat brain utilizing UV absorbance data. Compounds 4d , 4g , and 4j displayed encouraging anticonvulsant profile against both Seizure models with remarkably lower neurotoxicity. These compounds were found to increase the GABA level in rat brain significantly.

  • synthesis anticonvulsant and toxicity screening of newer pyrimidine semicarbazone derivatives
    European Journal of Medicinal Chemistry, 2010
    Co-Authors: Ozair Alam, Pooja Mullick, Surajpal Verma, Sadaf Jamal Gilani, S A Khan, Nadeem Siddiqui, Waquar Ahsan
    Abstract:

    Abstract A number of N -(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones ( 4a – t ) were synthesized and tested for their anticonvulsant activity against the two Seizure models, Maximal Electroshock Seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out.

  • Synthesis, anticonvulsant and toxicity screening of thiazolyl–thiadiazole derivatives
    Medicinal Chemistry Research, 2010
    Co-Authors: Nadeem Siddiqui, Waquar Ahsan
    Abstract:

    Various thiazole-substituted thiadiazole derivatives (7a–t) were designed and synthesized using substituted acetophenones and substituted anilines as starting materials. Thiazole and thiadiazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted Seizure models, Maximal Electroshock Seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Three compounds 7i, 7l and 7n were found to be potent in both the screens with comparable ED50 and better TD50 values than some standard drugs. These compounds were also found to exert lesser toxic effects on liver.

Prashant J Burange - One of the best experts on this subject based on the ideXlab platform.

Stanislaw J Czuczwar - One of the best experts on this subject based on the ideXlab platform.

  • influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse Maximal Electroshock Seizure model
    Pharmacological Reports, 2010
    Co-Authors: Krzysztof łukawski, Grazyna świderska, Jarogniew J łuszczki, Stanislaw J Czuczwar
    Abstract:

    Abstract The aim of this study was to determine whether ethacrynic acid (EA), a loop diuretic with anticonvulsant activity, would affect the protective action of the conventional antiepileptics (AEDs) carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and phenobarbital (PB) in the mouse Maximal Electroshock Seizure (MES) model. The effects of acute and chronic treatment with EA on these AEDs were examined. At a single dose of 100 mg/kg ip , EA enhanced the antiElectroshock activity of VPA, decreasing its ED 50 value from 225.6 to 146.6 mg/kg (p  50 values. The observed interaction between EA and VPA was pharmacodynamic in nature as EA did not alter free plasma (non-protein-bound) and total brain concentrations of VPA. Taking into consideration the clinical use of both drugs, this interaction between EA and VPA can be important for patients receiving these drugs.

  • effect of p isopropoxyphenylsuccinimide monohydrate on the anticonvulsant action of carbamazepine phenobarbital phenytoin and valproate in the mouse Maximal Electroshock induced Seizure model
    Pharmacological Reports, 2010
    Co-Authors: Jarogniew J łuszczki, Sergey L. Kocharov, Stanislaw J Czuczwar
    Abstract:

    This study was designed to determine the effects of p-isopropoxyphenylsuccinimide monohydrate (IPPS) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the mouse Maximal Electroshock Seizure model. Tonic hind limb extension (Seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. Results indicate that IPPS administered intraperitoneally (ip) at doses of 75 and 150 mg/kg significantly elevated the threshold for electroconvulsions in mice. IPPS at lower doses of 18.75 and 37.5 mg/kg had no impact on the threshold for electroconvulsions in mice. Moreover, 37.5 mg/kg IPPS significantly enhanced the anticonvulsant activity of phenytoin and valproate, but not that of carbamazepine or phenobarbital, in the Maximal Electroshock Seizure test in mice. IPPS (18.75 mg/kg) had no impact on the antiSeizure action of phenytoin and valproate against Maximal Electroshock-induced Seizures in mice. Pharmacokinetic experiments revealed that IPPS did not alter total brain concentrations of phenytoin or valproate in mice. In conclusion, the enhanced anticonvulsant action of phenytoin and valproate by IPPS in the mouse Maximal Electroshock-induced Seizure model and lack of pharmacokinetic interactions make the combinations of IPPS with phenytoin and valproate of pivotal importance for further experimental and clinical studies. The combinations of IPPS with carbamazepine and phenobarbital are neutral from a preclinical viewpoint.

  • Osthole suppresses Seizures in the mouse Maximal Electroshock Seizure model.
    European journal of pharmacology, 2009
    Co-Authors: Jarogniew J Luszczki, Marta Andres-mach, Wojciech Cisowski, Kazimierz Glowniak, Irena Mazol, Stanislaw J Czuczwar
    Abstract:

    The aim of this study was to determine the anticonvulsant effects of osthole {[7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one]--a natural coumarin derivative} in the mouse Maximal Electroshock-induced Seizure model. The antiSeizure effects of osthole were determined at 15, 30, 60, and 120 min after its systemic (i.p.) administration. Time course of anticonvulsant action of osthole revealed that the natural coumarin derivative produced a clear-cut antiElectroshock activity in mice and the experimentally-derived ED(50) values for osthole ranged from 259 to 631 mg/kg. In conclusion, osthole suppresses Seizure activity in the mouse Maximal Electroshock-induced Seizure model. It may become a novel treatment option following further investigation in other animal models of epilepsy and preclinical studies.

  • amiloride enhances the anticonvulsant action of various antiepileptic drugs in the mouse Maximal Electroshock Seizure model
    Journal of Neural Transmission, 2009
    Co-Authors: Jarogniew J Luszczki, Monika Dudrajastrzebska, Katarzyna M. Sawicka, Justyna Kozińska, Stanislaw J Czuczwar
    Abstract:

    Accumulating evidence indicates that amiloride (a potassium-sparing diuretic) exerts the anticonvulsant action in various in vivo and in vitro experiments. Therefore, the objective of this study was to assess the influence of amiloride on the protective action of numerous conventional and second-generation antiepileptic drugs [AEDs: carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), topiramate (TPM), and valproate (VPA)] against Maximal Electroshock (MES)-induced Seizures in mice. Results indicate that amiloride [up to 100 mg/kg, intraperitoneally (i.p.), at 30, 60, and 120 min before the test] neither altered the threshold for electroconvulsions, nor protected the animals against MES-induced Seizures in mice. Moreover, amiloride (75 and 100 mg/kg, i.p., 120 min prior to the test) significantly enhanced the anticonvulsant effects of all studied AEDs, except for LTG, by reducing their ED50 values in the MES test. In contrast, amiloride at 50 mg/kg (i.p.) had no significant effect on the antiElectroshock action of the tested AEDs in mice. Estimation of total brain AED concentrations revealed that amiloride (75 mg/kg) significantly increased total brain concentrations of CBZ, OXC, and PB, but not those of LTG, TPM, and VPA in mice. In conclusion, one can ascertain that the potentiation of the antiSeizure action of TPM and VPA by amiloride in the MES test and lack of any pharmacokinetic interactions between drugs, make the combinations of amiloride with TPM and VPA of pivotal importance for epileptic patients.

  • imperatorin enhances the protective activity of conventional antiepileptic drugs against Maximal Electroshock induced Seizures in mice
    European Journal of Pharmacology, 2007
    Co-Authors: Jarogniew J Luszczki, Kazimierz Glowniak, Stanislaw J Czuczwar
    Abstract:

    Abstract The effects of imperatorin (8-isopentenyloxypsoralen; 9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one) on the anticonvulsant activity of four conventional antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse Maximal Electroshock Seizure model. Results indicate that imperatorin (30 and 40 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against Maximal Electroshock-induced Seizures by reducing its median effective dose (ED 50 ) from 10.3 to 6.8 (by 34%; P P 50 values from 19.6 to 12.2 mg/kg (by 38%; P P