Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene

Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroant hracene (AMDA) and a structurally similar prototypical tricyclic amine imip ramine suggests that the two agents bind to the receptor in different fashi ons. The demonstration that AMDA is highly selective for serotonin receptor s (5-HT2A, K-i = 20 nM; 5-HT2c, K-i = 43 nM) versus the dopamine D-2 recept or (K-i >10,000 nM), as well as the serotonin and norepinephrine transporte rs (Ki >10,000 nM) further suggests that AMDA and the nonselective ligand i mipramine interact with these target macromolecules in different ways. (C) 2001 Elsevier Science Ltd. All rights reserved.