Tetrahydro-beta-carbolines and corresponding tryptamines: In vitro inhibition of serotonin, dopamine and noradrenaline uptake in rat brain synaptosomes.
The structure activity relationships of tryptolines and some other beta-carbolines and tryptamines as inhibitors of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) uptake were studied in rat brain synaptosomes. All beta-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-beta-carboline (5-hydroxytryptoline, 6-OH-THBC) with an IC50 of 5.0 x 10(-7) M at a 5-HT concentration of 10(-7) M. 6-Methoxy-tetrahydro-beta-carboline (5-methoxytryptoline) was slightly weaker; the inhibition of 5-HT uptake and DA uptake being competitive. Also tetrahydro-beta-carboline (tryptoline) was more potent than its 1-methylderivative, tetrahydroharmane (methtryptoline) or norharmane (beta-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 beta-carbolines, DA uptake, however, was inhibited better by 6-OH-THBC than by 5-HT or N-ME-T. Tetrahydro-beta-carbolines may inhibit 5-HT uptake also in vivo but is unlikely that catecholamine uptake is affected.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D007031:Hypothalamus / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism; D014363:Tryptamines / Q000378:metabolism*
D002243:Carbolines; D018492:Dopamine Antagonists; D007211:Indoles; D012702:Serotonin Antagonists; D014363:Tryptamines; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine