1,9-Alkano-Bridged 2,3,4,5-Tetrahydro-1H-3-benzazepines with Affinity for the α2-Adrenoceptor and the 5-HT1A Receptor

Article abstract of DOI:10.1021/jm00164a026

A number of 1,9-alkano-bridged 2,3,4,5-tetrahydro-1H-3-benzazepines were prepared and evaluated for 5-HT_1A receptor and α₂-adrenoceptor affinity by using radioligand receptor binding techniques.Several compounds displayed 5-HT_1A receptor affinity comparable to, or greater than, the known 5-HT_1A ligand buspirone.The highest affinity 5-HT_1A receptor ligands were N-alkyl-, N-allyl-5-chloro-, and 5-methoxy-1,2,3,4,8,9,10,10a-octahydronaphth<1,8-cd>azapines (4c, 4m, 4n), which had pK_i values of 7.9-8.1.The S enantiomer of 4c had a higher affinity for the 5-HT_1A receptor than the corresponding R isomer (pK_i of 8.2 for (S)-4c vs 7.7 for (R)-4c).These compounds had a relatively low affinity for the α₂-adrenoceptor (pK_i of 7 or less).On the other hand, the closely related 5-chloro-2-methyl-2,3,4,8,9,9a-hexahydro-1H-indeno<1.7-cd>azepine (3b) had high affinity for both the α₂-adrenoceptor (pK_i=8.1) and 5-HT_1A receptor (pK_i=7.6).These results indicate that the two receptors may share common recognition sites.