Synthesis, radioligand binding and molecular modeling studies of several 9-aminomethyl-9,10-dihydroanthracene (AMDA) analogs were carried out to determine the extent of the steric tolerance associated with expansion of the tricyclic ring system and amine substitution at 5-HT_2A and H₁ receptors. A mixture of (7,12-dihydrotetraphene-12-yl)methanamine and (6,11-dihydrotetracene-11-yl)methanamine in a 75–25% ratio was found to have an apparent K_i of 10 nM at the 5-HT_2A receptor. A substantial binding affinity for (7,12-dihydrotetraphene-3-methoxy-12-yl)methanamine at the 5-HT_2A receptor (K_i = 21 nM) was also observed. Interestingly, this compound was found to have 100-fold selectivity for 5-HT_2A over the H₁ receptor (K_i = 2500 nM). N-Phenylalkyl-AMDA derivatives, in which the length of the alkyl chain varied from methylene to n-butylene, were found to have only weak affinity for both 5-HT_2A and H₁ receptors (K_i = 223 to 964 nM). Our results show that large rigid annulated AMDA analogs can be sterically accommodated within the proposed 5-HT_2A binding site.

对几种 9-氨基甲基-9,10-二氢蒽 （AMDA） 类似物进行了合成、放射性配体结合和分子建模研究，以确定与三环系统的扩张和 5-HT_2A 和 H₁ 受体的胺取代相关的空间位阻耐受性程度。发现 （7,12-二氢四苯-12-基）甲胺和 （6,11-二氢四苯-11-基）甲胺的混合物以 75-25% 的比例在 5-HT_2A 受体处具有 10 nM 的表观 K。还观察到对 （7,12-二氢四苯-3-甲氧基-12-基）甲胺在 5-HT_2A 受体 （K = 21 nM） 处具有显著的结合亲和力。有趣的是，发现该化合物对 5-HT_2A 的选择性是 H₁ 受体的 100 倍 （K = 2500 nM）。发现 N-苯烷基-AMDA 衍生物的烷基链长度从亚甲基到正丁烯不等，对 5-HT_2A 和 H₁ 受体（K = 223 至 964 nM）仅具有较弱的亲和力。我们的结果表明，大的刚性环状 AMDA 类似物可以在拟议的 5-HT_2A 结合位点内空间容纳。