IN-VITRO EFFECT OF SOME 5-HYDROXY-INDOLALKYLAMINE DERIVATIVES ON MONOAMINE UPTAKE SYSTEM

Three different indolalkylamine derivatives (FA 102, FA 69, FA 70) hav ing in common an -OH group at 5 position of the indole ring and differ ing 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 oxi dase-A (MAO-A) [E.C.1.4.3.4] inhibitors. They were effective inhibitor s with, in some cases, similar potencies to clorgyline. ''In vitro'' e xperiments were performed on rat brain synaptosomes to investigate whe ther these MAO-A inhibitors had any effect on noradrenaline (NA), dopa mine (DA) and 5-hydroxytryptamine (5-HT) transport systems in differen t rat brain regions. The effect of these drugs were compared with thos e of clorgyline and 1-deprenyl. FA 102? FA 69, FA 70 behaved as inhibi tors of H-3-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 mu M, 60 mu M, 18 mu M for 5HT up take in cortex and 37 mu M, 55 mu M and 20 mu M in hippocampus; 70 mu M, 385 mu M, 695 mu M for NA uptake in cortex and 315 mu M, 255 mu M a nd 600 mu M in hypothalamus: 270 mu M, 160 mu M, 40 mu M for DA uptake in striatum, 1-Deprenyl was a very poor inhibitor of monoamine uptake , whereas clorgyline behaved similarly to these indolalkylamine deriva tives. Comparing these results with the IC50 values of citalopram, nis oxetine and GBR12909, specific and selective inhibitors of 5-HT, NA an d DA transport systems respectively, indicated that these indolalkylam ine derivatives interact more strongly with the 5HT uptake system.