Blockade of 45Ca2+ influx through the N-methyl-D-aspartate receptor ion channel by the non-psychoactive cannabinoid HU-211.
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.
Nadler
V
V
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Mechoulam
R
R
Sokolovsky
M
M
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015394:Molecular Structure; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D016194:Receptors, N-Methyl-D-Aspartate; D013759:Dronabinol; C062018:HU 211