Effects of the competitive NMDA receptor antagonist, CGP 37849, on anticonvulsant activity and adverse effects of valproate in amygdala-kindled rats
| Autor: | Wolfgang Löscher, Dagmar Hönack |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment CGP-37849 Pharmacology Receptors N-Methyl-D-Aspartate chemistry.chemical_compound Epilepsy Therapeutic index Seizures Internal medicine Convulsion Kindling Neurologic medicine Animals Rats Wistar business.industry Kindling Valproic Acid Antagonist Amygdala medicine.disease Rats Anticonvulsant Endocrinology 2-Amino-5-phosphonovalerate chemistry NMDA receptor Anticonvulsants Ataxia Female sense organs medicine.symptom business |
| Zdroj: | European Journal of Pharmacology. 234:237-245 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(93)90959-l |
| Popis: | The effects of combined treatment with low doses (1–5 mg/kg i.p.) of the competitive NMDA receptor antagonist, CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid), and the antiepileptic drug, valproate, were studied in amygdala-kindled and non-kindled rats. CGP 37849, 5 mg/kg, did not exert anticonvulsant effects in fully kindled rats but increased the anticonvulsant potency of valproate, 80 mg/kg i.p. However, the increase in anticonvulsant activity was parallelled by a marked increase in motor impairment, resulting in a considerable reduction of the therapeutic index of the combined treatment compared to valproate alone. Furthermore, at doses of 2.5–5 mg/kg, CGP 37849 potentiated the adverse effects but not the anticonvulsant activity of 50 mg/kg valproate. In non-kindled rats, combined treatment with CGP 37849 and valproate induced significantly less marked adverse effects than in kindled rats. The data on combined treatment with CGP 37849 and valproate substantiate that kindling alters the susceptibility to manipulations of NMDA receptor-mediated events. Since kindling is thought to be a predictive model of complex partial seizures, these results suggest that competitive NMDA receptor antagonists such as CGP 37849 may be of limited usefulness against this seizure type in humans. |
| Databáze: | OpenAIRE |
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