Costall B, Lim S K, Naylor R J, Cannon J G
J Pharm Pharmacol. 1982 Apr;34(4):246-54. doi: 10.1111/j.2042-7158.1982.tb04236.x.
Putative dopamine agonists from the 2-aminotetrahydronaphthalene and trans-octahydrobenzo (f) and (g) quinoline series were shown to inhibit the spontaneous locomotor activity of mice. Marked potency differences were observed between the alpha-and beta-rotameric conformations, compounds having the alpha-rotameric conformation having the greater potency. Thus, 2-di-n-propylmino-5,6-dihydroxytetrahydronaphthalene was 339 times more potent than the 6, 7-dihydroxy isomer, and 2-n-propylamino-5,6-dihydroxy-compound was respectively 79 times and 179 times more than 6,7-hydroxy-and 7,8-dihydroxycompounds. trans-7,8-dihydroxy-1-n-propyl-1,2,3,4,a,9,10,10b-octahydrobenzo(f)quinoline was 11 times more potent than the beta-rotamer, the 6,7-dihydroxy compound, and within the trans-octahydrobenzo(g)quinoline series the alpha-rotameric N-propyl derivative was 467 times more potent than the beta-rotamer, and the alpha-rotameric greater than N-H analogue was 46 fold more potent than the beta-rotamer. Thus, the alpha-rotamer appears the more potent in causing the present functional dopaminergic change. The dopaminergic nature of the response was indicated by its sensitivity to spiroperidol but not to yohimbine or prazosin. The possibility that a difference in behavioural potency between the alpha- and beta-rotamers may reflect a differential metabolism by catechol-O-methyl transferase was assessed by administration of different agonists after pyrogallol pretreatment. This potentiated the activity of 2-di-n-propylamino-6,7-dihydroxytetrahydro-naphthalene but not that of the 5,6-dihydroxy analogue. However, changes in the effects of N-propyl derivatives of trans-octahydrobenzo (f) and (g)quinoline were not marked and, in all experiments, pyrogallol treatment failed by orders of magnitude to shift the dose-response curves of the beta-rotamers to indicate a comparable potency to the rotameric forms.
来自2-氨基四氢萘以及反式八氢苯并(f)喹啉和(g)喹啉系列的推定多巴胺激动剂被证明可抑制小鼠的自发运动活性。在α-和β-旋转异构体构象之间观察到显著的效价差异，具有α-旋转异构体构象的化合物效价更高。因此，2-二正丙基氨基-5,6-二羟基四氢萘的效价比6,7-二羟基异构体高339倍，2-正丙基氨基-5,6-二羟基化合物分别比6,7-二羟基和7,8-二羟基化合物高79倍和179倍。反式-7,8-二羟基-1-正丙基-1,2,3,4,a,9,10,10b-八氢苯并(f)喹啉的效价比β-旋转异构体、6,7-二羟基化合物高11倍，在反式八氢苯并(g)喹啉系列中，α-旋转异构体N-丙基衍生物的效价比β-旋转异构体高467倍，α-旋转异构体大于N-H类似物的效价比β-旋转异构体高46倍。因此，α-旋转异构体在引起目前的功能性多巴胺能变化方面似乎更有效。该反应的多巴胺能性质通过其对螺哌啶醇敏感但对育亨宾或哌唑嗪不敏感来表明。通过在连苯三酚预处理后给予不同的激动剂，评估了α-和β-旋转异构体之间行为效价的差异可能反映儿茶酚-O-甲基转移酶不同代谢的可能性。这增强了2-二正丙基氨基-6,7-二羟基四氢萘的活性，但没有增强5,6-二羟基类似物的活性。然而，反式八氢苯并(f)喹啉和(g)喹啉的N-丙基衍生物的作用变化并不明显，并且在所有实验中，连苯三酚处理未能将β-旋转异构体的剂量反应曲线按数量级移动以表明与旋转异构体形式相当的效价。
