Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines

Abstract

The 5-HT1A and 5-HT2 receptor affinity of 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines 1-8, 10 and 12-15 has been determined. It has been found that the specific 5-HT1A affinity of the protonated form (KiAH+) 2-n-hexyl derivatives 4, 8, 14 and (+)-LSD is of the same order. It has been shown by means of molecular modelling methods that pharmacophores of all the active compounds can adopt a common position at the 5-HT1A receptor model. The model also offers an explanation for the observed stereoselectivity chiral compounds.