Pertwee R G, Fernando S R, Griffin G, Ryan W, Razdan R K, Compton D R, Martin B R
Department of Biomedical Sciences, Marischal College, University of Aberdeen, Scotland, UK.
Eur J Pharmacol. 1996 Nov 14;315(2):195-201. doi: 10.1016/s0014-2999(96)00631-0.
This investigation was directed at characterizing some of the pharmacological properties of 6'-cyanohex-2'-yne-delta 8-tetrahydrocannabinol (O-823), a compound with high affinity for cannabinoid binding sites (Ki = 0.77 nM). In mouse vasa deferentia, O-823 behaved as a potent partial cannabinoid CB1 receptor agonist (EC50 = 0.015 nM). In the guinea-pig myenteric plexus preparation, it antagonized WIN 55.212-2 [(R)-(+)-2,3-dihydro-5-methyl-3-[(4-morpholino)methyl]pyrrolo-[1,2,3-de ]-1, 4-benzoxazin-6-ylmethanone] and CP 55.940 [(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl ) cyclohexan-1-ol] with Kd values of 0.65 and 0.27 nM, respectively. After in vivo delta 9-tetrahydrocannabinol pretreatment. the sensitivity of vasa deferentia to O-823-induced inhibition of electrically evoked contractions was reduced by 127-fold. 3.162 nM O-823 was inhibitory in unpretreated vasa deferentia but antagonized CP 55,940 in pretreated tissues (Kd = 0.26 nM). O-823 is probably an antagonist in the myenteric plexus preparation and delta 9-tetrahydro-cannabinol pretreated vasa deferentia but a partial agonist in unpretreated vasa deferentia because the first two of these preparations contain fewer receptors than the third.
本研究旨在表征6'-氰基己-2'-炔-δ8-四氢大麻酚（O-823）的一些药理学特性，该化合物对大麻素结合位点具有高亲和力（Ki = 0.77 nM）。在小鼠输精管中，O-823表现为一种强效的部分大麻素CB1受体激动剂（EC50 = 0.015 nM）。在豚鼠肠肌丛制备物中，它拮抗WIN 55.212-2 [（R）-（+）-2,3-二氢-5-甲基-3-[(4-吗啉基)甲基]吡咯并-[1,2,3-de]-1,4-苯并恶嗪-6-基甲酮]和CP 55.940 [（-）-3-[2-羟基-4-(1,1-二甲基庚基)苯基]-4-(3-羟丙基)环己醇]，其解离常数（Kd）值分别为0.65和0.27 nM。在体内给予δ9-四氢大麻酚预处理后，输精管对O-823诱导的电诱发收缩抑制的敏感性降低了127倍。3.162 nM的O-823在未预处理的输精管中具有抑制作用，但在预处理的组织中拮抗CP 55,940（Kd = 0.26 nM）。O-823在肠肌丛制备物和δ9-四氢大麻酚预处理的输精管中可能是拮抗剂，但在未预处理的输精管中是部分激动剂，因为前两种制剂中的受体比第三种少。
