“In vitro” effect of some 5-hydroxy-indolalkylamine derivatives on monoamine uptake system

Summary

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 oxidaseA (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 5hydroxytryptamine (5-HT) transport systems in different rat brain regions. The effect of these drugs were compared with those of clorgyline and 1deprenyl. 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 μM, 60 μM, 18 μM for 5HT uptake in cortex and 37 μM, 55 μM and 20 μM in hippocampus; 70 μM, 385 μM, 695 μM for NA uptake in cortex and 315 μM, 255 μM and 600 μM in hypothalamus; 270 μM, 160 μM, 40 μM for DA uptake in striatum. l-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.