Wood L E, Daniels R, Bauer L, Gearien J E
J Pharm Sci. 1981 Feb;70(2):199-204. doi: 10.1002/jps.2600700222.
Isomers of the 2- and 9-aminobenzonorbornenes were prepared as rigid analogs of amphetamine and were employed to study the conformational requirements of indirectly acting sympathomimetic agents. Of this series of isomeric amines, the exo-2 and anti-9 isomers closely resemble the fully extended conformation of amphetamine. The other two amines, the endo-2 and syn-9 isomers, conformationally resemble the folded conformation of amphetamine. The isomers that resemble the extended conformation of amphetamine increased the spontaneous motor activity in mice while the isomers resembling the folded form either decreased or had no effect on motor activity. These compounds also were studied for their ability to accelerate the efflux of tritiated norepinephrine from vesicular and nonvesicular storage sites of isolated perfused rabbit atria; either alpha-methyl-p-tyrosine- or reserpine-pretreated rabbits were used. Amphetamine and the exo-2 and anti-9 isomers of aminobenzonorbornene could accelerate norepinephrine efflux from either compartment while the endo-2 and syn-9 isomers could accelerate the efflux from only the nonvesicular compartment at the concentrations studied. Fenfluramine and methylphenidate also were studied for their ability to accelerate efflux. Fenfluramine and methylphenidate resembled the aminobenzonorbornenes that correspond to the folded conformation of amphetamine in their ability to accelerate the efflux from nonvesicular storage. However, fenfluramine also resembled amphetamine and the aminobenzonorbornenes corresponding to the extended conformation of amphetamine in its ability to accelerate efflux from vesicular storage sites. The response to methylphenidate was similar to that of the aminobenzonorbornenes resembling the folded conformation of amphetamine.
制备了2-氨基和9-氨基苯并降冰片烯的异构体，作为苯丙胺的刚性类似物，用于研究间接作用拟交感神经药的构象要求。在这一系列异构胺中，外型-2和反式-9异构体与苯丙胺的完全伸展构象非常相似。另外两种胺，内型-2和顺式-9异构体，在构象上类似于苯丙胺的折叠构象。类似于苯丙胺伸展构象的异构体增加了小鼠的自发运动活性，而类似于折叠形式的异构体则降低或对运动活性没有影响。还研究了这些化合物加速氚化去甲肾上腺素从离体灌注兔心房的囊泡和非囊泡储存部位流出的能力；使用了α-甲基-p-酪氨酸或利血平预处理的兔子。苯丙胺以及氨基苯并降冰片烯的外型-2和反式-9异构体可以加速去甲肾上腺素从任一隔室流出，而在内型-2和顺式-9异构体在研究的浓度下只能加速非囊泡隔室的流出。还研究了芬氟拉明和哌醋甲酯加速流出的能力。芬氟拉明和哌醋甲酯在加速非囊泡储存流出的能力方面类似于对应于苯丙胺折叠构象的氨基苯并降冰片烯。然而，芬氟拉明在加速从囊泡储存部位流出的能力方面也类似于苯丙胺以及对应于苯丙胺伸展构象的氨基苯并降冰片烯。对哌醋甲酯的反应类似于类似于苯丙胺折叠构象的氨基苯并降冰片烯的反应。
