Carney J M, Balster R L, Martin B R, Harris L S
J Pharmacol Exp Ther. 1979 Sep;210(3):399-404.
The effects of a number of cannabinoids in squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation were determined after intraperitoneal (i.p.) and intraventricular (i.v.t.) administration. The order of potency was (+/-)-9-nor-9 beta-OH hexahydrocannabinol, 11-OH-delta 9-tetrahydrocannabinol, delta 9-tetrahydrocannabinol (delta 9-THC), cannabinol and cannabidiol. (+/-)-9-Nor-9 alpha-OH-hexahydrocannabinol was inactive at doses up to 3 mg/kg i.p. and 0.1 mg/kg i.v.t. Although the order of potency was the same by both routes of administration, the i.v.t./i.p. potency ratio differed markedly. This demonstrates the importance of route of administration in assessing structure-activity relationships of cannabinoids and suggests that differences in penetration to the central nervous system may be an important determinant of behavioral activity. Although 11-OH-delta 9-THC was more potent than the parent compound delta 9-THC by both routes, the potency difference was less after i.v.t. administration. It was also demonstrated that metabolic conversion of [3H]delta 9-THC does not take place in squirrel monkey brain when administered i.v.t. which could account for the direct i.v.t. effects of delta 9-THC. These observations suggest that metabolic conversion of delta 9-THC in the liver is not necessary for its behavioral effects.
在松鼠猴经腹腔注射（i.p.）和脑室内注射（i.v.t.）后，测定了多种大麻素对按固定间隔 - 固定比率链式食物呈现时间表进行反应训练的松鼠猴的影响。效力顺序为（±）-9 - 去甲 - 9β - 羟基六氢大麻酚、11 - 羟基 - δ9 - 四氢大麻酚、δ9 - 四氢大麻酚（δ9 - THC）、大麻酚和大麻二酚。（±）-9 - 去甲 - 9α - 羟基 - 六氢大麻酚在腹腔注射剂量高达3 mg/kg和脑室内注射剂量高达0.1 mg/kg时无活性。虽然两种给药途径的效力顺序相同，但脑室内注射/腹腔注射效力比差异显著。这证明了给药途径在评估大麻素构效关系中的重要性，并表明对中枢神经系统渗透的差异可能是行为活性的重要决定因素。虽然11 - 羟基 - δ9 - 四氢大麻酚在两种给药途径下都比母体化合物δ9 - 四氢大麻酚更有效，但脑室内注射后的效力差异较小。还证明了[3H]δ9 - 四氢大麻酚经脑室内注射给药时在松鼠猴脑中不发生代谢转化，这可以解释δ9 - 四氢大麻酚的直接脑室内注射效应。这些观察结果表明，δ9 - 四氢大麻酚在肝脏中的代谢转化对于其行为效应并非必要。
