Add time:07/23/2019         Source:sciencedirect.com

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 κ-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 κ-opioid and the glycine/NMDA receptors during epileptic phenomena.

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