Anticonvulsant effects of dextrorphan in rats: possible involvement in dextromethorphan-induced seizure protection.
Anticonvulsant effects of dextrorphan in rats: possible involvement in dextromethorphan-induced seizure protection.
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右啡烷对大鼠的抗惊厥作用：可能参与右美沙芬诱导的癫痫发作保护。
DOI：
10.1016/0024-3205(88)90350-5
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发表时间：
1988
期刊：
影响因子：
6.1
通讯作者：
M. Pontecorvo
中科院分区：
文献类型：
--
作者：
F. Tortella;J. Ferkany;M. Pontecorvo
非阿片类抗惊厥药/止咳药美沙芬的主要代谢产物是右啡烷。在本研究中，在癫痫发作活动（最大电休克惊厥）（MES）的实验模型中确定了右啡烷的作用。皮下注射右啡烷可产生剂量相关的强直性后肢伸展阻滞（THE）和强直性前肢伸展持续时间缩短（TFE）。右啡烷的抗惊厥作用是线性的，并且最有效。与原型抗惊厥药物二苯基海因相比，右啡烷的效力高2.5倍（ED 50分别为30μmol/kg和12μmol/kg）。预处理。纳洛酮不能拮抗右旋糖酐诱导的THE阻滞。此外，用右旋糖酐预处理未能显著增强苯乙内酰脲的抗惊厥效力。右啡烷的抗惊厥作用可能与其对苯环利定/N-甲基-D-天冬氨酸受体复合物的作用有关，而美沙芬的抗惊厥作用归因于与大脑中特定美沙芬位点的结合。因此，我们认为，虽然右啡烷的代谢可能有助于右美沙芬的抗惊厥作用，但它可能是通过一种不相关的受体机制实现的。
The major metabolite of the non-opioid anticonvulsant/antitussive dextromethorphan is dextrorphan. In the present study, the effects of dextrorphan were determined in an experimental model of seizure activity (maximal electroshock convulsions) (MES). Subcutaneous administration of dextrorphan produced dose-related blockade of tonic hindlimb extension (THE) and a decrease in the duration of tonic forelimb extension (TFE). The anticonvulsant effect of dextrorphan was linear and maximally efficacious. Compared to the prototypical anticonvulsant drug diphenylhydantoin, dextrorphan was 2.5 times more potent (ED50's= 30μmol/kg and 12μmol/kg, respectively). Pretreatment. with naloxone failed to antagonize dextrorphan-induced blockade of THE. Moreover, pretreatment with dextrophan failed to significantly enhance the anticonvulsant potency of diphenylhydantoin. It is likely that the anticonvulsant effects of dextrorphan are related to its actions at the phencyclidine/N-methyl-D-aspartate receptor complex, whereas the anticonvulsant effects of dextromethorphan have been attributed to binding to a specific dextromethorphan site in the brain. Therefore, we suggest that while metabolism to dextrorphan could possibly contribute to the anticonvulsant effects of dextromethorphan, it is probably through an unrelated receptor mechanism.
苯环己哌啶类药物对小鼠的抗惊厥特性。
影响因子：
5
作者：
Hayes,BA;Balster,RL
通讯作者：
Balster,RL
豚鼠大脑中的高亲和力右美沙芬结合位点。
影响因子：
3.6
作者：
Craviso,GL;Musacchio,JM
通讯作者：
Musacchio,JM
豚鼠大脑中的高亲和力右美沙芬结合位点。
影响因子：
3.6
作者：
Craviso,GL;Musacchio,JM
通讯作者：
Musacchio,JM