Nadler V, Mechoulam R, Sokolovsky M
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Brain Res. 1993 Sep 17;622(1-2):79-85. doi: 10.1016/0006-8993(93)90804-v.
The effects of the synthetic non-psychoactive cannabinoid (+)-(3S,4S)-7-hydroxy-delta 6-tetrahydrocannabinol 1,1-dimethylheptyl (HU-211) on the activity of the N-methyl-D-aspartate (NMDA) receptor/ion channel were examined. HU-211 non-competitively blocks the increase in binding of [3H]N-[1-(2-thienyl)-cyclohexyl]piperidine ([3H]TCP) induced by the polyamines spermine and spermidine or by glutamate and glycine. HU-211 does not, however, affect the direct binding of [3H]glycine and [3H]glutamate to their binding sites on the NMDA receptor, which suggests that the effects of HU-211 are not mediated via the binding sites of glutamate-, glycine- and phencyclidine-like drugs or of polyamines. HU-211 can also block 45Ca2+ uptake through the NMDA-receptor/ion channel in primary cell cultures of rat forebrain. All of the above inhibitory effects of HU-211 on the NMDA-receptor/ion channel activity are stereospecific, since the (-)(3R,4R) enantiomer (HU-210) is ineffective.
研究了合成的非精神活性大麻素（+）-（3S，4S）-7-羟基-δ6-四氢大麻酚1,1-二甲基庚基（HU-211）对N-甲基-D-天冬氨酸（NMDA）受体/离子通道活性的影响。HU-211非竞争性地阻断了多胺精胺和亚精胺或谷氨酸和甘氨酸诱导的[3H]N-[1-（2-噻吩基）-环己基]哌啶（[3H]TCP）结合增加。然而，HU-211并不影响[3H]甘氨酸和[3H]谷氨酸与它们在NMDA受体上的结合位点的直接结合，这表明HU-211的作用不是通过谷氨酸、甘氨酸和苯环利定样药物或多胺的结合位点介导的。HU-211还可以阻断大鼠前脑原代细胞培养物中通过NMDA受体/离子通道的45Ca2+摄取。HU-211对NMDA受体/离子通道活性的所有上述抑制作用都是立体特异性的，因为（-）（3R，4R）对映体（HU-210）无效。
