"In vitro" effect of some 5-hydroxy-indolalkylamine derivatives on monoamine uptake system.

Abstract

Three different indolalkylamine derivatives (FA 102, FA 69, FA 70) having in common an -OH group at 5 position of the indole ring and differing in the presence of a methyl group at the N or the acetylenic group of the side chain, have been synthesized and assayed as monoamine oxidase-A (MAO-A) [E.C.1.4.3.4] inhibitors. They were effective inhibitors with, in some cases, similar potencies to clorgyline. "In vitro" experiments were performed on rat brain synaptosomes to investigate whether these MAO-A inhibitors had any effect on noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) transport systems in different rat brain regions. The effect of these drugs were compared with those of clorgyline and 1-deprenyl. FA 102, FA 69, FA 70 behaved as inhibitors of 3H-monoamine uptake with similar rank of order of potency for amine uptake inhibition: 5-HT > DA > NA. The IC50 values for FA 102, FA 69, FA 70, respectively, were: 17 microM, 60 microM, 18 microM for 5HT uptake in cortex and 37 microM, 55 microM and 20 microM in hippocampus; 70 microM, 385 microM for NA uptake in cortex and 315 microM, 255 microM and 600 microM in hypothalamus; 270 microM, 160 microM, 40 microM for DA uptake in striatum. 1-Deprenyl was a very poor inhibitor of monoamine uptake, whereas clorgyline behaved similarly to these indolalkylamine derivatives. Comparing these results with the IC50 values of citalopram, nisoxetine and GBR12909, specific and selective inhibitors of 5-HT, NA and DA transport systems respectively, indicated that these indolalkylamine derivatives interact more strongly with the 5HT uptake system.