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-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, Ki=20 nM; 5-HT2C, Ki=43 nM) versus the dopamine D2 receptor (Ki>10,000 nM), as well as the serotonin and norepinephrine transporters (Ki>10,000 nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.