Glennon R A, McKenney J D, Lyon R A, Titeler M
J Med Chem. 1986 Feb;29(2):194-9. doi: 10.1021/jm00152a005.
1-(2,5-Dimethoxy-4-bromophenyl)-2-aminopropane (DOB; 1a) is a purported serotonin (5-HT) agonist that binds selectively to central 5-HT2 binding sites. Systematic removal of any or all of the aromatic substituents had relatively little effect on 5-HT1 binding but reduced 5-HT2 binding by approximately 2 or more orders of magnitude. Demethylation of the 2-methoxy group of 1a, or introduction of an N-n-propyl group, doubled 5-HT1-site affinity but decreased 5-HT2-site affinity by 3- and 30-fold, respectively. In tests of stimulus generalization, using rats trained to discriminate DOM from saline, the 2-demethyl and N-propyl derivatives were found to produce stimulus effects similar to those of DOB. In addition, the S-(+) isomer of the iodo analogue of 1a was found to possess one-third the affinity of its R-(-) enantiomer at 5-HT2 sites and also resulted in DOM-stimulus generalization. Of the DOB analogues examined, DOB (1a) possesses optimal selectivity for 5-HT2 binding.
1-(2,5-二甲氧基-4-溴苯基)-2-氨基丙烷（DOB；1a）是一种据称的血清素（5-HT）激动剂，它选择性地结合中枢5-HT2结合位点。系统地去除任何或所有芳香取代基对5-HT1结合的影响相对较小，但使5-HT2结合降低了约2个或更多数量级。1a的2-甲氧基去甲基化或引入N-正丙基，使5-HT1位点亲和力加倍，但5-HT2位点亲和力分别降低了3倍和30倍。在刺激泛化测试中，使用经训练能区分DOM和生理盐水的大鼠，发现2-去甲基和N-丙基衍生物产生的刺激效应与DOB相似。此外，发现1a的碘代类似物的S-(+)异构体在5-HT2位点的亲和力是其R-(-)对映体的三分之一，并且也导致了DOM刺激泛化。在所研究的DOB类似物中，DOB（1a）对5-HT2结合具有最佳选择性。
