Enhancement of 5-hydroxytryptamine (5-HT, serotonin) neurotransmission is a viable means of treating depression. On the basis of this observation, agents that inhibit re-uptake of 5-HT were prepared based on (−)-cocaine and aryltropanes as lead compounds because they are reasonably potent 5-HT re-uptake inhibitors. Molecular dissection of an aryltropane provided a series of 5-and 6-membered ring compounds. From among this library of ...