Carranza Gómez-Carpintero M, Ochoa Estomba M C
Department of Research, Laboratorios Morrith, S. A., Madrid, Spain.
Arzneimittelforschung. 1993 Sep;43(9):937-41.
The biochemical properties of the new methyl indole derivative IM-24 (N-methyl-N-propargyl-2(1-methyl-5-methoxyindolyl)methylamine HCl) have been investigated. The activity on both forms of monoamine oxidase MAO was tested in several nervous and non nervous tissues ex vivo after chronic administration. IM-24 is mainly an inhibitor of the activity of MAO A without any effect on intestinal MAO B at the doses studied. IM-24 was compared with tricyclic antidepressants in tests for serotonin (5HT), noradrenaline (NA) and dopamine (DA) uptake inhibition in vitro. IM-24 is mainly an inhibitor of the 5HT uptake mechanism but is less active than paroxetine and chlorimipramine which are very potent 5HT-uptake inhibitors. Radioligand binding techniques in rat brain ex vivo showed that IM-24 after chronic administration (21 days) produces no change in the number or the affinity of the alpha 2-adrenoceptors. IM-24 reduces by 70% the number of 5HT2 receptors but does not modify the affinity for the ligand. IM-24 is thus an interesting compound which combines monoamine oxidase inhibition with inhibition of 5HT uptake. Both these actions will lead to an increase of the availability of serotonin at the synaptic site.
对新型甲基吲哚衍生物IM-24（N-甲基-N-炔丙基-2(1-甲基-5-甲氧基吲哚基)甲胺盐酸盐）的生化特性进行了研究。在慢性给药后，于多种神经和非神经组织中对单胺氧化酶MAO两种形式的活性进行了离体测试。在所研究的剂量下，IM-24主要是MAO A活性的抑制剂，对肠道MAO B没有任何影响。在体外进行的5-羟色胺（5HT）、去甲肾上腺素（NA）和多巴胺（DA）摄取抑制试验中，将IM-24与三环类抗抑郁药进行了比较。IM-24主要是5HT摄取机制的抑制剂，但活性低于帕罗西汀和氯米帕明，后两者是非常有效的5HT摄取抑制剂。在大鼠脑内进行的离体放射性配体结合技术显示，慢性给药（21天）后，IM-24对α2-肾上腺素能受体的数量或亲和力没有影响。IM-24使5HT2受体数量减少70%，但不改变对配体的亲和力。因此，IM-24是一种有趣的化合物，它将单胺氧化酶抑制与5HT摄取抑制结合在一起。这两种作用都将导致突触部位5-羟色胺的可用性增加。
