Selectivity of Sterically Fixed Tryptamine and 5‐Methoxytryptamine Derivatives for Serotonin Receptor Subtypes, II :Structure‐Activity Relationships and in vitro Pharmacology of N ‐Alkyl‐ and N,N ‐Dialkyl‐3‐indolylbicyclo‐[2.2.1]‐heptane‐2‐amines

Twentyfour norbornane analogues of tryptamine and 5‐methoxytryptamine were investigated for affinity at 5‐HT 2 receptors of the rat tail artery and proved to be weak non‐competitive antagonists of 5‐HT. Compound 12 which displayed a marked depression of the concentration‐effect curves, was examined for potential interaction with the allosteric binding site of the 5‐HT 2 receptor. The effects elicited by 12 , in the presence and absence of the allosteric activator ketanserin, were atpyical and must be attributed to a mechanism, unknown up to now. In radioligand displacement experiments binding data for a set of nine compounds were determined at 5‐HT 1 ‐ like, 5‐HT 2 and 5‐HT 3 receptors, indicating subtype selectivity for some analogues. The binding affinity of 8 at 5‐HT 3 receptors which was comparable with the affinity of the selective 5‐HT 3 agonist 2‐methyl‐5‐HT, could not be demonstrated on the longitudinal muscle strip of the guineapig ileum. partially due to the M 3 antimuscarinic activity of 8 . Functional studies on the rat oesophagal tunica muscularis mucosae did not reveal 5‐HT 4 agonist properties for two analogues of 5‐methoxytryptamine ( 8, 16 ).