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

Abstract

Tetrahydro-P-carbolines (THBCs), 6-methoxyharmalan and norharman and the corresponding open chain tryptamines studied inhibited 5-hydroxytryptamine (5-HT) and dopamine (DA) uptake in human blood platelets. I-methyl-THBCs were better inhibitors of D A than 5-HT uptake but THBCs generally were far more potent inhibitors of 5-HT uptake than of DA uptake. 6-methoxy-1,2,3,4-tetrahydro-P-carboline was as potent as 5-HT itself in 'H-5-HT uptake inhibition in platelets and the inhibition wascompetitive. All the P-carbolines studied were more potent inhibitors of 'H-DA uptake than DA itself. Contrary to results in rat brain synaptosomes, THBCs were more potent in platelets than the corresponding tryptamines with the freely rotating ethylamine side chain. Unsaturated P-carbolines were weaker inhibitors than THBCs. The clear difference in the rank order of potencies of these compounds in human platelets and rat brain synaptosomes demonstrates that these different model systems for amine uptake studies d o not always give comparable results. The results also suggest that there are differences in the uptake systems for 5-HT and D A in human platelets.

Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

“…BCs have a wide variety of pharmacological effects including the inhibition of plasmalemmal dopamine transport, inhibition of MAO, and, perhaps the most unusual, inverse agonism of GABA A receptors at the benzodiazepine site [222,223]. Like some TIQs, it has been thought that BCs impact addiction and neurodegeneration: in vitro, BCs have been shown to act as plasmalemmal and vesicular uptake inhibitors of serotonin and dopamine, and, in vivo, can reduce striatal serotonin and dopamine concentrations, and lead to bradykinesia [224][225][226]. Conversely, one BC, pinoline, has been postulated to confer protective effects from oxidative stress [227].…”

Drug–drug interactions involving classic psychedelics: A systematic review

“…Ayahuasca brew is usually made from a plant containing DMT and another plant that contains β-carbolines which mostly inhibit MAO-A, thereby making DMT orally active ( McKenna, 2004 ). Tetrahydroharmine (THH), one of the β-carbolines present in the brew, can also act as a weak serotonin uptake inhibitor and increase brain serotonin levels ( Airaksinen et al, 1980 ). Fluoxetine strongly inhibits the CYP2D6 enzyme, which metabolises many drugs, including serotonin.…”