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Background. To compare the anticonvulsant potency of 10 various p-isopropoxyphenylsuccinimide (IPPS) derivatives [i.e., IPPS (IPPS); N-(morpholinomethyl)-IPPS (MM-IPPS); N-(anilinomethyl)-IPPS (AM-IPPS); N-hydroxymethyl-IPPS (HM-IPPS); N-(p-acetylphenyl)-IPPS (AP-IPPS); N-(p-ethoxycarbonylphenylmethyl)-IPPS (ECPM-IPPS); N-(m-bromoanilinomethyl)-IPPS (BAM-IPPS); N-(o-carboxyanilinomethyl)-IPPS (o-CAMIPPS); N-(m-carboxyanilinomethyl)-IPPS (m-CAM-IPPS); N-(p-carboxyanilinomethyl)-IPPS (p-CAM-IPPS)] in the maximal electroshock-induced seizure threshold (MEST) test in mice. Material and methods. Linear regression analysis of doses of IPPS derivatives and their threshold increases in the MEST test in mice allowed to calculate TID20 values i.e., doses of the tested IPPS derivatives that elevate by 20% the seizure threshold in IPPS-treated mice over the threshold in control animals. Results. A ll t he studied IPPS derivatives (i.e., IPPS, MMIPPS, HM-IPPS, AP-IPPS, AM-IPPS, ECPM-IPPS, o-CAM-IPPS, m-CAM-IPPS, p-CAM-IPPS and BAM-IPPS) increased in a dose dependent manner the threshold for maximal electroshockinduced seizures in mice. The TID20 values in the MEST test for IPPS, AP-IPPS, AM-IPPS, BAMIPPS, o-CAM-IPPS, m-CAM-IPPS, p-CAM-IPPS, ECPM-IPPS, HM-IPPS, and MM-IPPS were 60.44 mg/kg, 86.30 mg/kg, 44.69 mg/kg, 103.34 mg/kg, 22.43 mg/kg, 52.84 mg/kg, 80.85 mg/kg, 109.75 mg/kg, 32.62 mg/kg and 53.50 mg/kg, respectively. Conclusions. The studied IPPS derivatives with respect to their anticonvulsant potency in the MEST test can be arranged as follows: o-CAM-IPPS > HM-IPPS > AM-IPPS > m-CAM-IPPS > MM-IPPS > IPPS > p-CAM-IPPS >AP-IPPS > BAM-IPPS > ECPM-IPPS.
The present study was designed to investigate the influence of acute ethanol intake and its withdrawal on the anticonvulsant effect of alpha-tocopherol in penicillin-induced epileptiform activity. Ethanol-treated rats received a daily dose of 3 g/kg or 9.0 g/kg of 30% ethanol solution for 3 days. Thirty minutes after penicillin injection (500 units, i.c.), the most effective dose of alpha-tocopherol (500 mg/kg) was administered intramuscularly (i.m.). Acute administration of ethanol, in a dose of 3 g/kg, did not change either frequency or amplitude of penicillin-induced epileptiform activity, while dose of 9 g/kg ethanol significantly decreased the mean frequency of penicillin-induced epileptiform ECoG activity in the ethanol-treated group. Ethanol (9 g/kg) withdrawal also caused an increase in the amplitude of epileptiform ECoG activity in the withdrawal group. The results suggest that acute administration of high dose ethanol (9 g/kg) and alpha-tocopherol have some limited anticonvulsive effects in penicillin-induced epileptiform activity in rats.
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.
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