Tetrahydro-beta-carbolines and corresponding tryptamines: In vitro inhibition of serotonin and dopamine uptake by human blood platelets.
Tetrahydro-beta-carbolines (THBCs), 6-methoxyharmalan and norharman and the corresponding open chain tryptamines studied inhibited t-hydroxytrypere better inhibitors of DA 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-beta-carboline was as potent as 5-HT itself 3H-5-HT uptake inhibition in platelets and the inhibition was competitive. All the beta-carbolines studied were more potent inhibitors of 3h-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 beta-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 do not always give comparable results. The results also suggest that there are differences in the uptake systems for 5-HT and DA in human platelets.
D001792:Blood Platelets / Q000378:metabolism; D002243:Carbolines / Q000494:pharmacology*; D004298:Dopamine / Q000097:blood; D018492:Dopamine Antagonists; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000494:pharmacology*
D002243:Carbolines; D018492:Dopamine Antagonists; D007211:Indoles; D012702:Serotonin Antagonists; D014363:Tryptamines; D012701:Serotonin; D004298:Dopamine