Jirkovsky I, Humber L G, Voith K, Charest M P
Arzneimittelforschung. 1977;27(9):1642-8. doi: 10.1002/chin.197751242.
A series of novel 1,3,4,9-tetrahydro-1-methyl-thiopyrano-[3,4-b]indole-1-ethanamines has been synthesized and examined for effects on reserpine-induced ptosis and reserpine-induced hypothermia in mice. One member of the series, the 9-ethyl-N,N-dimethyl derivative V (tandamine), was selected for further studies in regard to its possible use as an antidepressant agent. Tandamine has been resolved, and the levorotatory enantiomer was found to be more active than the racemic compound. The N-desmethyl derivative XIII, a metabolite of tandamine, has been prepared. The 5-ethyl-1,3,4,5-tetrahydro-N,N,1-trimethylthiopyrano[4,3-b]indole-1-ethanamine XXI, an analog of tandamine with the isomeric ring system, has also been synthesized and evaluated. In the primary pharmacological screening and in the drug-interaction studies with reserpine, tetrabenazine, and tremorine, tandamine was compared to the clinically effective tricyclic antidepressants--desipramine, imipramine, and amitriptyline. Tandamine was more effective than these agents in several screening procedures indicative of potential antidepressant activity.
已合成了一系列新型的1,3,4,9-四氢-1-甲基-硫代吡喃并[3,4-b]吲哚-1-乙胺，并研究了它们对小鼠利血平诱导的眼睑下垂和利血平诱导的体温过低的影响。该系列中的一个成员，即9-乙基-N,N-二甲基衍生物V（坦达明），因其可能用作抗抑郁药而被选作进一步研究。坦达明已被拆分，发现左旋对映体比外消旋化合物更具活性。已制备了坦达明的代谢产物N-去甲基衍生物XIII。还合成并评估了5-乙基-1,3,4,5-四氢-N,N,1-三甲基硫代吡喃并[4,3-b]吲哚-1-乙胺XXI，它是具有异构环系统的坦达明类似物。在主要的药理学筛选以及与利血平、丁苯那嗪和震颤素的药物相互作用研究中，将坦达明与临床有效的三环抗抑郁药——地昔帕明、丙咪嗪和阿米替林进行了比较。在一些表明潜在抗抑郁活性的筛选程序中，坦达明比这些药物更有效。
