569351-28-6Relevant articles and documents
Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors
Khorana, Nantaka,Smith, Carol,Herrick-Davis, Kathy,Purohit, Anil,Teitler, Milt,Grella, Brian,Dukat, Ma?gorzata,Glennon, Richard A.
, p. 3930 - 3937 (2003)
On the basis of an earlier finding that 5-methyl-5H-1,2,3,4-tetrahydropyrido[4,3-b]indole (5-methyl-1,2,3,4-tetrahydro-γ-carboline; 1) binds at murine 5-HT 5A receptors, preliminary structure-affinity studies were conducted. The present investigation extends these structure-affinity studies using human 5-HT5A receptors and examined additional analogues of 1. It was found (a) that there is little interspecies difference for the affinities of these compounds, (b) that an intact 1,2,3,4-tetrahydro-γ-carboline ring system seems optimal and an N2-(3-(substituted-phenoxy)propyl) moiety results in high affinity, (c) that structurally related 1,2,3,4-tetrahydro-β-carbolines also bind at 5-HT5A receptors, and (d) that all examined derivatives also possess affinity for 5-HT 2A receptors. Evidence is provided that 5-HT5A and 5-HT2A receptor affinities probably do not covary and that it might be possible, with continued investigation, to develop analogues with enhanced 5-HT5A selectivity.
