非精神活性大麻素可作为一种功能性N-甲基-D-天冬氨酸受体阻滞剂。
Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.
作者信息
Feigenbaum J J, Bergmann F, Richmond S A, Mechoulam R, Nadler V, Kloog Y, Sokolovsky M
机构信息
Brettler Medical Research Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
出版信息
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9584-7. doi: 10.1073/pnas.86.23.9584.
Abstract
Binding studies using the enantiomers of the synthetic cannabinoid 7-hydroxy-delta 6-tetrahydrocannabinol 1,1-dimethylheptyl homolog in preparations of rat brain cortical membranes reveal that the (+)-(3S,4S) enantiomer HU-211 blocks N-methyl-D-aspartate (NMDA) receptors in a stereospecific manner and that the interaction occurs at binding sites distinct from those of other noncompetitive NMDA antagonists or of glutamate and glycine. Moreover, HU-211 induces stereotype and locomotor hyperactivity in mice and tachycardia in rat, effects typically caused by NMDA receptor antagonists. HU-211 is also a potent blocker of NMDA-induced tremor, seizures, and lethality in mice. This compound may therefore prove useful as a nonpsychoactive drug that protects against NMDA-receptor-mediated neurotoxicity.
摘要
使用合成大麻素7-羟基-δ6-四氢大麻酚1,1-二甲基庚基同系物的对映体在大鼠脑皮质膜制剂中进行的结合研究表明，(+)-(3S,4S)对映体HU-211以立体特异性方式阻断N-甲基-D-天冬氨酸（NMDA）受体，且这种相互作用发生在与其他非竞争性NMDA拮抗剂或谷氨酸和甘氨酸不同的结合位点。此外，HU-211在小鼠中诱导刻板行为和运动性多动，在大鼠中诱导心动过速，这些效应通常由NMDA受体拮抗剂引起。HU-211也是NMDA诱导的小鼠震颤、癫痫发作和致死性的有效阻滞剂。因此，这种化合物可能被证明是一种有用的非精神活性药物，可预防NMDA受体介导的神经毒性。
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