SELECTIVITY OF STERICALLY FIXED TRYPTAMINE AND 5-METHOXYTRYPTAMINE DERIVATIVES FOR SEROTONIN RECEPTOR SUBTYPES .2. STRUCTURE-ACTIVITY-RELATIONSHIPS AND IN-VITRO PHARMACOLOGY OF N-ALKYL- AND -DIALKYL-3-INDOLYLBICYCLO-[2.2.1]-HEPTANE-2-AMINES

Twentyfour norbornane analogues of tryptamine and 5-methoxytryptamine were investigated for affinity at 5-HT2 receptors of the rat tail arte ry and proved to be weak non-competitive antagonists of 5-HT. Compound 12 which displayed a marked depression of the concentration-effect cu rves, was examined for potential interaction with the allosteric bindi ng site of the 5-HT2 receptor. The effects elicited by 12, in the pres ence and absence of the allosteric activator ketanserin, were atpyical and must be attributed to a mechanism, unknown up to now. In radiolig and displacement experiments binding data for a set of nine compounds were determined at 5-HT1-like, 5-HT2 and 5-HT3 receptors, indicating s ubtype selectivity for some analogues. The binding affinity of 8 at 5- HT3 receptors which was comparable with the affinity of the selective 5-HT3 agonist 2-methyl-5-HT, could not be demonstrated on the longitud inal muscle strip of the guineapig ileum, partially due to the hi, ant imuscarinic activity of 8. Functional studies on the rat oesophageal t unica muscular-is mucosae did not reveal 5-HT4, agonist properties for two analogues of 5-methoxytryptamine (8, 16).