Trans-2-(2,5-dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT 2 receptor family

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4- iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT 2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (-)-(1R,2S)- configuration. Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT 2A and 5-HT 2B receptors. Therefore, at appropriate doses - although (-)-4 and (-)-5 may be useful as tools to probe 5-HT 2 receptor function - one would need to be mindful that their selectivity for 5-HT 2A receptors is somewhat less than for DOI itself