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      Anticonvulsant Effect of Antiaris toxicaria (Pers.) Lesch. (Moraceae) Aqueous Extract in Rodents

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          Abstract

          Antiaris toxicaria (Moraceae) was evaluated for anticonvulsant activity in rodents. Animal models used include maximal electroshock test (MEST); pentylenetetrazole-induced (PTZ) convulsions; picrotoxin-induced (PCT) convulsions; strychnine- (STR-) and 4-aminopyridine-induced convulsions. Increase in latency to seizures as well as reduction in duration and frequency of seizures indicated anticonvulsant activity. The extract was more effective in all models used except the maximal electroshock test and strychnine-induced convulsions. Antiaris toxicaria aqueous extract (200, 400, and 800 mg kg −1) significantly ( P < 0.05 − 0.01) shortened the duration of convulsions in PTZ- and PCT-induced seizures. Delay in the onset of convulsions in the two tests was significant ( P < 0.001). Reduction in the frequency of seizures was also significant ( P < 0.05 − 0.001) in both tests. Antiaris further delayed the onset of seizures in 4-aminopyridine model while producing 75% protection against death in mice. Diazepam (0.1, 0.3, and 1 mg kg −1), carbamazepine (3, 10, and 30 mg kg −1), and sodium valproate (100–400 mg kg −1) were used as reference anticonvulsant drugs for various models. Flumazenil blocked the effect of the extract in the PTZ test significantly suggesting that Antiaris toxicaria may be acting by enhancing the effects of the GABAergic system. Antiaris toxicaria aqueous extract therefore possesses anticonvulsant activity.

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          Guide for the care and use of laboratory animals.

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            The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models.

            Although seizure models using electrical stimulation for the induction of generalized tonic-clonic seizures in rodents are widely employed to identify potential anticonvulsants, the important role of various technical, biological and pharmacological factors in the interpretation of results obtained with these models is often not recognized. The aim of this study was to delineate factors other than sex, age, diet, climate and circadian rhythms, which are generally known. For this purpose, experiments with 8 clinically established antiepileptic drugs were undertaken in the following electroshock seizure models: (1) the maximal (tonic extensor) electroshock seizure threshold (MEST) in mice; (2) the traditional maximal electroshock seizure (MES) test with supra-threshold stimulation in mice; and (3) the MES test with suprathreshold stimulation in rats. When drugs were dissolved in vehicles which did not themselves exert effects on seizure susceptibility, the most important factors which influenced drug potencies were (1) marked differences between drugs and species in terms of peak drug effect, duration of action and the formation of active metabolites; (2) differences in drug potencies calculated on the basis of administered doses compared to potency calculations based on active drug concentrations; (3) the equipment used for seizure induction; (4) marked effects of current strength on results obtained in electroshock seizure models; (5) site of application of the electrical stimulus (transcorneal vs. transauricular). In order to reduce the variability among estimates of anticonvulsant activity, the various factors delineated in this study should be rigidly controlled in experimental situations involving assay of anticonvulsant agents.
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              Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations.

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                Author and article information

                Journal
                ISRN Pharmacol
                ISRN Pharmacol
                ISRN.PHARMACOLOGY
                ISRN Pharmacology
                Hindawi Publishing Corporation
                2090-5165
                2090-5173
                2013
                18 September 2013
                : 2013
                : 519208
                Affiliations
                1Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                2Department of Pharmacology, University of Ghana Medical School, University of Ghana, Accra, Ghana
                3Department of Biomedical and Forensic Sciences, School of Biological Science, University of Cape Coast, Cape Coast, Ghana
                Author notes

                Academic Editors: C.-G. Jang, A. Pittaluga, and B.-N. Wu

                Author information
                http://orcid.org/0000-0002-2182-5736
                Article
                10.1155/2013/519208
                3791639
                24167736
                7d4b1a15-9962-4233-ada2-de55cafd0d9c
                Copyright © 2013 Priscilla Kolibea Mante et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 June 2013
                : 13 August 2013
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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