Tetrahydro‐β‐carbolines and Corresponding Tryptamines: In Vitro Inhibition of Serotonin, Dopamine and Noradrenaline Uptake in Rat Brain Synaptosomes

Abstract

The structure activity relationships of tryptolines and some other β-carbolines and tryptamines as inhibitors of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) uptake were studied in rat brain synaptosomes. All β-carbolines inhibited to higher degree the uptake of 5-HT than that of DA or NA (IC50's 5–100 times lower). The most potent tryptoline derivative was 6-hydroxy-tetrahydro-β-carboline (5-hydroxytryptoline, 6-OH-THBC) with an IC50 of 5.0× 10^-7M at a 5-HT concentration of 10^-7M. 6-Methoxy-tetrahydro-β-carboline (5-methoxytryptoline) was slightly weaker; the inhibition of 5-HT uptake and DA uptake being competitive. Also tetrahydro-β-carboline (tryptoline) was more potent than its 1-methylderivative, tetrahydroharmane (methtryptoline) or norharmane (β-carboline). All of them were, however, weaker inhibitors of 5-HT uptake than the freely rotating indoleamines N-methyl-tryptamine (N-Me-T) or 5-HT itself. N-Me-T and 5-HT were also more potent inhibitors of DA and NA uptake than most of the β-carbolines, DA uptake, however, was inhibited better by 6-OH-THBC than by 5-HT or N-Me-T. Tetrahydro-β-carbolines may inhibit 5-HT uptake also in vivo but it is unlikely that catecholamine uptake is affected.