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 P-carbolines and tryptamines as inhibitors of serotonin (5-HT). dopamine (DA) and noradrenaline (NA) uptake were studied in rat brain synaptosomes. All P-carbolines inhibited to higher degree the uptake of 5-HT than that of D A or NA (IC50's 5-100 times lower). The most potent tryptoline derivative was 6-hydroxy-tetrahydro-P-carboline (5-hydroxytryptoline, 6-OH-THBC) with an IC50 of 5.OX IO-'M at a 5-HT concentration of IO-'M. 6-Methoxy-tetrahydro-P-carboline (5-methoxytryptoline) was slightly weaker; the inhibition of 5-HT uptake and DA uptake being competitive. Also tetrahydro-P-carboline (tryptoline) was more potent than its 1-methylderivative, tetrahydroharmane (methtryptoline) or norharmane (P-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 and5-HT were also more potent inhibitors of D A and NA uptake than most of the P-carbolines, DA uptake, however, was inhibited better by 6-OH-THBC than by 5-HT or N-Me-T. Tetrahydro-P-carbolines may inhibit 5-HT uptake also in vivo but it is unlikely that catecholamine uptake is affected.

Tetrahydro‐β‐carbolines and Corresponding Tryptamines: In Vitro Inhibition of Serotonin and Dopamine Uptake by Human Blood Platelets

“…3) Pyridine ring unsaturation decreased potency: BC is slightly weaker than THBC. Our results were similar also in synaptosomes (Komulainen et a/. 1980) and contrary to those of Rommelspacher et a/.…”

“…In rat striatal synaptosomes 6-MeO-THBC and I-Me-6-MeO-THBC are weaker inhibitors than congeners without a methoxy substitution. A hydroxy group increased potency in striatal synaptosomes (Komulainen et a/. 1980) as in rat brainstem synaptosomes (Tuomisto & Tuomisto 1973).…”

Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms

“…[18] Furthermore, tetrahydro-b-carbolines do not inhibit MAO A, yet represent neuroactive natural products as well as they moderately inhibits erotonin reuptake. [19] Conclusions Psilocybe mushrooms produce an ayahuasca-like andp otentially similarly synergistic set of metabolites that may impact upon onset and duration of their effects. Remarkably, both pathways originate from the same generic building block, ltryptophan, yet take different routes leading to dissimilar compoundsw hose bioactivities in return contributedirectly and indirectly to the same pharmacology (Scheme 1).…”

“…Human placental MAO A is inhibited at K i =7.2 μ m . Furthermore, tetrahydro‐β‐carbolines do not inhibit MAO A, yet represent neuroactive natural products as well as they moderately inhibit serotonin reuptake …”

LIGHT MICROSCOPIC AUTORADIOGRAPHY OF RAT RETINAE AFTER INTRAVITREAL INJECTION OF [3H]6‐METHOXY‐TETRAHYDRO‐β‐CARBOLINE

“…One of the major biochemical effects of 6-MeO-THBC seems to be the inhibition of 5-HT uptake and the increase of free 5-HT in brain (Komulainen et al 1980). 6-MeO-THBC has also been shown to inhibit the uptake and promote the release of 5-HT in the retina (Thomas et al 1979).…”