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Jarogniew J Luszczki - One of the best experts on this subject based on the ideXlab platform.
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effect of xanthotoxin 8 methoxypsoralen on the anticonvulsant activity of classical antiepileptic drugs against maximal Electroshock induced Seizures in mice
Fitoterapia, 2015Co-Authors: Miroslaw Zagaja, Michal Glensk, Kazimierz Glowniak, Daniel Pyrka, Krystyna Skalickawozniak, Magdalena Florekluszczki, Jarogniew J LuszczkiAbstract:Abstract The effects of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse maximal Electroshock Seizure model. Tonic hind limb extension (Seizure activity) was evoked in adult male albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Results indicate that xanthotoxin (50 and 100 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against maximal Electroshock-induced Seizures (P In conclusion, the combinations of xanthotoxin with carbamazepine and valproate, despite their beneficial effects in terms of Seizure suppression in mice, were probably due to a pharmacokinetic increase in total brain concentrations of these antiepileptic drugs in experimental animals.
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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, 2010Co-Authors: Jarogniew J Luszczki, Monika Dudrajastrzebska, Piotr Czuczwar, Anna Cioczekczuczwar, Marta AndresmachAbstract: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.
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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, 2009Co-Authors: Jarogniew J Luszczki, Ewa Wojda, Marta Andres-mach, Wojciech Cisowski, Michal Glensk, Kazimierz GlowniakAbstract: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.
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N-(anilinomethyl)-p-isopropoxyphenylsuccinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal Electroshock-induced Seizure model.
Neuroscience Research, 2009Co-Authors: Jarogniew J Luszczki, Sergey L. KocharovAbstract: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.
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Osthole suppresses Seizures in the mouse maximal Electroshock Seizure model.
European journal of pharmacology, 2009Co-Authors: Jarogniew J Luszczki, Marta Andres-mach, Wojciech Cisowski, Irena Mazol, Kazimierz GlowniakAbstract: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.
Kazimierz Glowniak - One of the best experts on this subject based on the ideXlab platform.
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effect of xanthotoxin 8 methoxypsoralen on the anticonvulsant activity of classical antiepileptic drugs against maximal Electroshock induced Seizures in mice
Fitoterapia, 2015Co-Authors: Miroslaw Zagaja, Michal Glensk, Kazimierz Glowniak, Daniel Pyrka, Krystyna Skalickawozniak, Magdalena Florekluszczki, Jarogniew J LuszczkiAbstract:Abstract The effects of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse maximal Electroshock Seizure model. Tonic hind limb extension (Seizure activity) was evoked in adult male albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Results indicate that xanthotoxin (50 and 100 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against maximal Electroshock-induced Seizures (P In conclusion, the combinations of xanthotoxin with carbamazepine and valproate, despite their beneficial effects in terms of Seizure suppression in mice, were probably due to a pharmacokinetic increase in total brain concentrations of these antiepileptic drugs in experimental animals.
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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, 2009Co-Authors: Jarogniew J Luszczki, Ewa Wojda, Marta Andres-mach, Wojciech Cisowski, Michal Glensk, Kazimierz GlowniakAbstract: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.
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Osthole suppresses Seizures in the mouse maximal Electroshock Seizure model.
European journal of pharmacology, 2009Co-Authors: Jarogniew J Luszczki, Marta Andres-mach, Wojciech Cisowski, Irena Mazol, Kazimierz GlowniakAbstract: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.
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imperatorin enhances the protective activity of conventional antiepileptic drugs against maximal Electroshock induced Seizures in mice
European Journal of Pharmacology, 2007Co-Authors: Jarogniew J Luszczki, Kazimierz GlowniakAbstract: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
Jarogniew J. Łuszczki - One of the best experts on this subject based on the ideXlab platform.
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influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal Electroshock Seizure model
Pharmacological Reports, 2010Co-Authors: Krzysztof łukawski, Grazyna świderska, Jarogniew J. ŁuszczkiAbstract: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.
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Influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal Electroshock Seizure model
Pharmacological Reports, 2010Co-Authors: Krzysztof łukawski, Grażyna Świderska, Jarogniew J. ŁuszczkiAbstract: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.
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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, 2010Co-Authors: Jarogniew J. Łuszczki, Sergey L. KocharovAbstract: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.
Sergey L. Kocharov - One of the best experts on this subject based on the ideXlab platform.
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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, 2010Co-Authors: Jarogniew J. Łuszczki, Sergey L. KocharovAbstract: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.
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N-(anilinomethyl)-p-isopropoxyphenylsuccinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal Electroshock-induced Seizure model.
Neuroscience Research, 2009Co-Authors: Jarogniew J Luszczki, Sergey L. KocharovAbstract: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.
James P Stables - One of the best experts on this subject based on the ideXlab platform.
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cyclization of the semicarbazone template of aryl semicarbazones synthesis and anticonvulsant activity of 4 5 diphenyl 2h 1 2 4 triazol 3 4h one
Biomedicine & Pharmacotherapy, 2009Co-Authors: Martina Shalini, Perumal Yogeeswari, Dharmarajan Sriram, James P StablesAbstract:Abstract A new series of 4,5-diphenyl-2 H -1,2,4-triazol-3(4 H )-one were synthesized to study the effect of cyclization of the semicarbazone moiety of aryl semicarbazones on the anticonvulsant activity. Structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. All compounds were evaluated for their anticonvulsant activity in four animal models of Seizures, viz. maximal Electroshock Seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and subcutaneous picrotoxin (scPIC)-induced Seizure threshold tests. The compounds were also evaluated for neurotoxicity. Compounds 4 , 9 , 14 – 19 exhibited anticonvulsant activity in all the four animal models of Seizure.
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2 4 dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of Seizures synthesis and pharmacological evaluation
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Rathinasabapathy Thirumurugan, James P Stables, Dharmarajan Sriram, Amrita Saxena, Perumal YogeeswariAbstract:Abstract Various 2,4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4-dimethoxyaniline via a phenylcarbamate intermediate. The structures were confirmed by spectral and elemental analyses. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three Seizure models in mice which include maximal Electroshock Seizure, subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced Seizure screens. Nine compounds exhibited protection in all the three Seizure models, and N 1 -(2,4-dimethoxyphenyl)- N 4 -(propan-2-one)semicarbazone ( 17 ) emerged as the most active compound with no neurotoxicity. These compounds were found to elevate γ-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions equipotent to clobazam.
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3 chloro 2 methylphenyl substituted semicarbazones synthesis and anticonvulsant activity
ChemInform, 2004Co-Authors: Perumal Yogeeswari, James P Stables, Rathinasabapathy Thirumurugan, Ramkumar Kavya, Jayakar Selwyn Samuel, Dharmarajan SriramAbstract:A series of 3-chloro-2-methylphenyl substituted semicarbazones (3-33) was synthesized and evaluated for anticonvulsant and CNS activities. After intraperitoneal injection to mice or rats, the semicarbazone derivatives were examined in the maximal Electroshock Seizure (MES), subcutaneous pentylenetetrazole (scPTZ), and subcutaneous strychnine (scSTY)-induced Seizure and neurotoxicity screens. The aryl urea (1) and the semicarbazide (2) showed anticonvulsant activity in the MES and scPTZ screens with acute neurotoxicity, whereas the semicarbazone derivatives showed good anticonvulsant potency in the scSTY screen with moderate activity against MES and scPTZ screens. Compound 21 exhibited anticonvulsant potency against all the three screens with lesser neurotoxicity. Some titled compounds exhibited lesser CNS depression and neurotoxicity compared to phenytoin or carbamazepine as was evident from the CNS studies.
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An in vivo evaluation of the antiSeizure activity and acute neurotoxicity of agmatine
Pharmacology Biochemistry and Behavior, 2003Co-Authors: Aimee K. Bence, James P Stables, David R. Worthen, Peter A. CrooksAbstract:Agmatine, an endogenous cationic amine, exerts a wide range of biological effects, including modulation of glutamate-activated N-methyl-D-aspartate (NMDA) receptor function in the central nervous system (CNS). Since glutamate and the NMDA receptor have been implicated in the initiation and spread of Seizure activity, the capacity of agmatine to inhibit Seizure spread was evaluated in vivo. Orally administered agmatine (30 mg/kg) protected against maximal Electroshock Seizure (MES)-induced Seizure spread in rats as rapidly as 15 min and for as long as 6 h after administration. Inhibition of MES-induced Seizure spread was also observed when agmatine was administered intraperitoneally. Agmatine's antiSeizure activity did not appear to be dose-dependent. An in vivo neurotoxicity screen indicated that agmatine was devoid of any acute neurological toxicity at the doses tested. These preliminary data suggest that agmatine has promising anticonvulsant activity.
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synthesis and anticonvulsant activity of 4 bromophenyl substituted aryl semicarbazones
European Journal of Medicinal Chemistry, 2000Co-Authors: S N Pandeya, Perumal Yogeeswari, James P StablesAbstract:Abstract A number of 4-bromophenyl semicarbazones were synthesised and evaluated for anticonvulsant and sedative–hypnotic activities. After intraperitoneal injection to mice, the semicarbazone derivatives were examined in the maximal Electroshock Seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY) and neurotoxicity (NT) screens. All the compounds showed anticonvulsant activity in one or more test models. Compound 12 showed greatest activity, being active in all the screens with very low neurotoxicity and no sedative–hypnotic activity. All the compounds except 7 had lower neurotoxicity compared to phenytoin. Three compounds ( 6, 11 and 14 ) showed greater protection than sodium valproate. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore.