The competitive NMDA receptor antagonists CGP 37849 and CGP 39551 are potent, orally-active anticonvulsants in rodents
| Autor: | C. Portet, H. R. Olpe, Roland Heckendorn, Annick Vassout, Graham E. Fagg, H. van Riezen, A. Jeker, Klaus Klebs, Hans Allgeier, Markus Schmutz |
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| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_treatment CGP-37849 Mice Inbred Strains Pharmacology Receptors N-Methyl-D-Aspartate Mice chemistry.chemical_compound Oral administration Competitive NMDA Receptor Antagonists Kindling Neurologic medicine Animals Postural Balance ED50 Electroshock Chemistry Kindling Rats Inbred Strains General Medicine Rats Receptors Neurotransmitter Anticonvulsant Orally active 2-Amino-5-phosphonovalerate Pentylenetetrazole NMDA receptor Anticonvulsants sense organs |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 342:61-66 |
| ISSN: | 1432-1912 0028-1298 |
| Popis: | Anticonvulsant properties of CGP 37849 and CGP 39551, two novel phosphono-amino acids which are competitive NMDA receptor antagonists, were examined in rodents. At optimal pretreatment times CGP 37849 suppressed electroshock-induced seizures in mice and rats with ED50s ranging from 8 to 22 mg/kg after oral administration, and 0.4 to 2.4 mg/kg after i. v. and i. p. injection. Relative to CGP 37849, CGP 39551 was more potent after p. o. (ED50 3.7–8.1 mg/kg), and less potent after i.v. or i.p. treatment (ED50 2.7–8.7 mg/kg). Following oral treatment, the duration of action of CGP 37849 was about 8 h, while CGP 39551 still showed good activity after 24 h (ED50 8.7 mg/kg, mouse; 21 mg/kg, rat). Both compounds were anticonvulsant at doses below those at which overt behavioural side effects were apparent. CGP 39551 delayed the development of kindling in rats at doses of 10 mg/kg p. o. and above, and showed weak anticonvulsant activity against pentylenetetrazolevoked seizures. CGP 37849 and CGP 39551 are the first competitive NMDA antagonists to show oral anticonvulsant properties in a therapeutically-useful dose-range, and hence are interesting candidates for novel antiepileptic therapy in man. |
| Databáze: | OpenAIRE |
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