Pars H G, Granchelli F E, Razdan R K, Keller J K, Teiger D G, Rosenberg F J, Harris L S
J Med Chem. 1976 Apr;19(4):445-54. doi: 10.1021/jm00226a001.
Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.
通过早期通讯中描述的一般方法合成了多种δ6a,10a-四氢大麻酚的氮类似物。在将化合物溶于聚乙二醇200中静脉给药后，通过改良的欧文小鼠筛选法测定了最小有效剂量（MED50）和致死剂量（LD50）。最有效的化合物是炔丙基（5t）、烯丙基（5m）和氯烯丙基（5o-q）衍生物。发现5t和罗杰·亚当斯的碳环类似物（III）在小鼠、猫、狗和猴子身上的明显行为效应（中枢神经系统抑制、静态共济失调和超敏反应）相似。二氯异丙肾上腺素可预防并逆转III和5t的许多抑制作用，但对这些化合物产生的共济失调无影响。在抗伤害感受测试中，5t在苯醌和埃迪热板测试中具有活性，但在甩尾测试中无活性。
