Antiparkinsonian drugs memantine and trihexyphenidyl potentiate the anticonvulsant activity of valproate against maximal electroshock-induced seizures
| Autor: | Waldemar A. Turski, Czuczwar Sj, Zdzisław Kleinrok, Marek Dziki, Urbańska Em |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Trihexyphenidyl medicine.medical_treatment Pharmacology Antiparkinson Agents Cellular and Molecular Neuroscience Mice Memantine Memory Seizures Convulsion Avoidance Learning Medicine Animals Chemotherapy Antiparkinsonian drugs Electroshock business.industry Valproic Acid Long-term potentiation Drug Synergism Maximal electroshock Anticonvulsant Anticonvulsants medicine.symptom business Psychomotor Performance medicine.drug |
| Zdroj: | Neuropharmacology. 31(10) |
| ISSN: | 0028-3908 |
| Popis: | Memantine increased the threshold for electroconvulsions, when administered at 1.0–6.0 mg/kg (i.p.) and given in subthreshold dosesof 0.0156, 0.0625, 0.125 and 0.5 mg/kg (i.p.) potentiated the protective efficacy of valproate, against maximal electroshock (50 mA)-induced seizures in mice, lowering the ED 50 from 235 to 197, 172, 164 and 130 mg/kg, respectively. Trihexyphenidyl, applied in doses of 30 and 50 mg/kg (i.p.), did not influence the electroconvulsive threshold per se but when combined with valproate, strongly enhanced its anticonvulsant activity against maximal electroshock-induced seizures lowering the ED 50 from 206 to 103 and 46 mg/kg, respectively. The chimney test and retention testing in mice revealed that administration of memantine at 0.5 mg/kg (i.p.) or trihexyphenidyl at 30 mg/kg (i.p.) together with valproate in doses of 130 or 103 mg/kg (i.p.), respectively, resulted in motor impairmeny and caused impairment of long-term memory, similar to the effects of valproate alone, when applied at its ED 50 against maximal electroshock. Neither memantine nor trihexyphenidyl altered the total level of valproate in plasma. It may be concluded that the potentiation of the anticonvulsant activity of valproate, by memantine and trihexyphenidyl, is not associated with a pharmacokinetic interaction. |
| Databáze: | OpenAIRE |
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