Eli Lilly and Co.'s decision to abandon Sepracor Inc.'s R-fluoxetine version of Prozac due to cardiovascular side effects raises questions about whether the strategy of removing the "bad" isomers of drugs to obtain improved chemical entities (ICEs) is as straightforward as it seems.

A risk in developing ICEs is that when second- or third-generation drugs are discovered, taking out the bad player of a first generation drug may not do the trick in terms of beating the competition. In the case of R-fluoxetine, this was likely to happen. New understanding about the roles of serotonin, norepinephrine and dopamine in depression means that mixed action drugs can be seen to give