FROM SERENDIPITY TO SELECTIVITY

Most reference antidepressants were discovered in the 1950s by serendi pity and not as a result of knowledge of the mechanism of action or of a predictive pharmacological profile. During the 1960s, the principal effects of the older psychotropic drugs on neurotransmitters were ide ntified. This led to two biochemical theories of depression being prop osed, one involving the noradrenergic system and the other the seroton ergic system. Most drugs however, interacted with both systems, and th e few that demonstrated selectivity showed no corresponding difference s in terms of clinical use. Two strategic approaches were adopted for the development of new compounds in the 1970s. One involved the select ive inhibition of MAO-A or MAO-B and on the reversibility of the inter action with MAO. The second strategy was to develop selective serotoni n reuptake inhibitors (SSRIs). These SSRIs appear equally effective to older compounds and are virtually devoid of interaction with the rece ptors of other systems such that side effects are either mild or absen t.