2,3-dihydro and carbocyclic analogues of tryptamines: interaction with serotonin receptors

Several dihydro and carbocyclic analogues of tryptamine were evaluated in order to determine the role of the heterocyclic portion of the indole nucleus on the interaction of indolealkylamines with the serotonin receptors of the rat fundus. Reduction of the C2--C3 double bond or replacement of the indole nitrogen with an sp3-hybridized carbon atom results in a 50% decrease in receptor affinity. Complete removal of the five-membered ring of N,N-dimethyltryptamine reduces affinity by an order of magnitude. It appears that an intact indole nucleus, though not entirely necessary, results in an optimal receptor interaction for the indolealkylamines examined.