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1.
Gen Pharmacol ; 24(2): 439-47, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8387056

RESUMO

1. The effects of U-54494A and U-50488H on convulsions produced by sound have been studied in genetically epilepsy-prone DBA/2 mice and genetically epilepsy-prone rats. 2. Both compounds showed a dose-dependent anticonvulsant activity. U-54494A was less potent as an anticonvulsant than U-50488H in genetically epilepsy-prone rats and elicited a similar potency to that of U-50488H in DBA/2 mice when administered intracerebroventricularly or intraperitoneally. 3. Similar sedative and hypothermic effects were observed after the highest dose of U-54494A and U-50488H in DBA/2 mice. U-50488H seems to exhibit a greater sedative effect and to affect the rotarod test in rats much more than U-54494A. U-54494A elicited a better therapeutic index than U-50488H. 4. The anticonvulsant properties of both compounds are antagonized by high doses of naloxone and nor-binaltorphimine, a selective kappa-opioid antagonist. 5. The effects of U-50488H and U-54494A in DBA/2 mice were also antagonized by the glycine/NMDA receptor antagonist D-serine. 6. The present results suggest a possible interaction between kappa-opioid and the glycine/NMDA receptors during epileptic phenomena.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/prevenção & controle , Pirrolidinas/uso terapêutico , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de Neurotransmissores/efeitos dos fármacos , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos DBA , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Pirrolidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Glicina , Receptores de N-Metil-D-Aspartato/fisiologia , Receptores de Neurotransmissores/fisiologia , Receptores Opioides kappa/efeitos dos fármacos , Serina/farmacologia
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