1,2,3,4-tetrahydroisoquinoline derivatives: A new class of 5-HT1A receptorligands

Three series of new N-substituted 1,2,3,4-tetrahydroisoquinolines with 2-, 3-, and 4-membered alkyl chains (a, b, and c, respectively) were synthesize d, and the effect of some structural modifications on their 5-HT1A receptor affinities and functional properties was discussed. It was found that the volume of the terminal amide substituent was a crucial parameter which dete rmined 5-HT1A receptor affinities of the tested compounds, while the in viv o activity seemed to depend on both the R-volume and the length of a hydroc arbon chain. It was demonstrated that the most active ligands behaved like agonists or partial agonists at post synaptic 5-HT1A receptors. (C) 1999 El sevier Science Ltd. All rights reserved.