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

100%

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.

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Assessment of combined treatment with vigabatrin and antihypertensive drugs against electroconvulsions in mice

80%

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.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Journal of Pre-Clinical and Clinical Research

2 Czuczwar S. J.

1 Borowicz K. K.

1 Lukawski K.

1 Raszewski G.

1 Sawulski C.

1 Swiader M.

1 Turski W. A.

1 Zgrajka W.

1 2015

1 2002

Wyniki wyszukiwania

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

Assessment of combined treatment with vigabatrin and antihypertensive drugs against electroconvulsions in mice