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SYM 2206 (a potent non-competitive AMPA receptor antagonist) elevates the threshold for maximal electroshock-induced seizures in mice

100%
Luszczki J. J., Leszkowicz M., Kondrat-Wrobel M. W., Florek-Luszczki M.
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vol. 27
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issue 2
80-83
EN
The aim of this study was to determine the effect of SYM 2206 (a potent non-competitive AMPA receptor antagonist) on the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions were produced in mice by means of a current (sinewave, 50 Hz, maximum 500 V, strength from 4 to 14 mA, 0.2-s stimulus duration, tonic hind limb extension taken as the endpoint) delivered via ear-clip electrodes. SYM 2206 administered systemically (i.p.), 30 min before the MEST test, at doses of 2.5 and 5 mg/kg, did not alter the threshold for maximal electroconvulsions in mice. In contrast, SYM 2206 at doses of 10 and 20 mg/kg significantly elevated the threshold for maximal electroconvulsions in mice (P<0.01 and P<0.001). Linear regression analysis of SYM 2206 doses and their corresponding threshold increases allowed for the determination of threshold increasing doses by 20% and 50% (TID20 and TID50 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 and TID50 values for SYM 2206 were 4.25 and 10.56 mg/kg, respectively. SYM 2206 dose-dependently increased the threshold for MEST-induced seizures, suggesting the anticonvulsant action of the compound in this seizure model in mice.
2
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Effect of N-(m-bromoanilinomethyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

76%
Luszczki J. J., Marzeda E., Kondrat-Wrobel M. W., Pyrka D., Kocharov S. L., Florek-Luszczki M.
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vol. 27
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issue 2
76-79
EN
The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl)- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock (MES)-induced tonic 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 ear-clip electrodes. BAM-IPPS administered (i.p.) at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice (P<0.05). Lower doses of BAM-IPPS (50 and 100 mg/kg) had no significant impact on the threshold for electroconvulsions in mice. Moreover, BAM-IPPS (100 mg/kg) did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the mouse MES model. BAM-IPPS elevated the threshold for electroconvulsions in mice in a dosedependent manner. However, BAM-IPPS (100 mg/kg) did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of BAM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.
3
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Synergistic interaction of levetiracetam with gabapentin in the mouse 6 Hz psychomotor seizure model – a type II isobolographic analysis

76%
Wlaz A., Kondrat-Wrobel M. W., Zaluska K., Kochman E., Rekas A. R., Luszczki J. J.
Current Issues in Pharmacy and Medical Sciences
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2015
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vol. 28
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issue 3
204-207
EN
This study was aimed at characterizing the anticonvulsant effects of levetiracetam in combination with gabapentin, in the mouse 6 Hz psychomotor seizure model. Herein, psychomotor seizures were evoked in male albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Type II isobolographic analysis was used to characterize the anticonvulsant interactions between the drugs in combination, for fixed-ratios of 1:1, 1:2, 1:5 and 1:10. The type II isobolographic analysis revealed that the combinations of levetiracetam with gabapentin for the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; P<0.05) in terms of seizure suppression, while the combinations for the fixed-ratios of 1:1 and 1:2 were additive in the mouse 6 Hz psychomotor seizure model. We conclude that, as the combinations of levetiracetam with gabapentin for the fixed-ratios of 1:5 and 1:10 exerted supra-additive (synergistic) interaction in the mouse 6 Hz psychomotor seizure model, this may be considered as particularly favorable combinations in further clinical practice.
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