诺布啡烷对N-甲基-D-天冬氨酸诱导的惊厥和死亡的保护作用。

Norbinaltorphimine protection against N-methyl-D-aspartic acid-induced convulsions and mortality.

作者信息

Shukla V K, Lemaire S

机构信息

Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.

出版信息

Eur J Pharmacol. 1993 Feb 9;231(2):293-6. doi: 10.1016/0014-2999(93)90463-r.

DOI:10.1016/0014-2999(93)90463-r

PMID:7681005

Abstract

The kappa-selective opioid antagonist, norbinaltorphimine (Nor-BNI), was tested against convulsions and mortality induced by the excitatory amino acids, N-methyl-D-aspartic acid (NMDA), (R,S)-alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid and the gamma-aminobutyric acid antagonist, bicuculline. Nor-BNI (10-40 nmol; intracerebroventricularly, i.c.v.) protected against NMDA (0.5-2.0 nmol i.c.v.)-induced convulsions and NMDA (2 nmol i.c.v.) and AMPA (2 nmol i.c.v.)-induced mortality. The opioid antagonist, naloxone (10 nmol i.c.v.), had no protecting activity. In vitro, Nor-BNI competed with the binding of the specific NMDA receptor ligand, [3H]D,L-(E)-2-amino-4-propyl- 5-phosphono-3-pentenoic acid ([3H]CGP 39653, 10 nM; IC50 of 1.63 +/- 0.20 microM) to mouse brain membrane preparations. The results indicate that the protecting activities of Nor-BNI are mediated by NMDA receptor-related mechanisms.

摘要

对κ-选择性阿片样物质拮抗剂诺布那托啡胺（Nor-BNI）进行了测试，观察其对由兴奋性氨基酸N-甲基-D-天冬氨酸（NMDA）、（R，S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和红藻氨酸以及γ-氨基丁酸拮抗剂荷包牡丹碱所诱导的惊厥和死亡的影响。Nor-BNI（10 - 40纳摩尔；脑室内注射，i.c.v.）可预防NMDA（0.5 - 2.0纳摩尔i.c.v.）诱导的惊厥以及NMDA（2纳摩尔i.c.v.）和AMPA（2纳摩尔i.c.v.）诱导的死亡。阿片样物质拮抗剂纳洛酮（10纳摩尔i.c.v.）没有保护活性。在体外，Nor-BNI可与特异性NMDA受体配体[3H]D，L-（E）-2-氨基-4-丙基-5-膦酰基-3-戊烯酸（[3H]CGP 39653，10纳摩尔；IC50为1.63±0.20微摩尔）与小鼠脑膜制剂的结合发生竞争。结果表明，Nor-BNI的保护活性是由NMDA受体相关机制介导的。