Drug Design and Emotion

?Geteiltes Leid ist halbes Leid?

  The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take a literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. How does this sharing happen? Visual perception of suffering may be important but also narrative description plays a role. All of our other senses are mixing in.

  Antidepressants and other therapeutics are another choice to change the state of emotion. Their development follows the today?s notion of ?rationality? in the design of therapeutics and is characterized by an atomic resolution approach to understanding drug activity.

  Since emotional states and physiological states are entangled and given the difficulty of physical description of emotion, the question will be raised whether or not, and if, how far a future rational design should encompass mental states. 

  A ligand is not a drug, is not a drug, is not a drug. What we are facing today is the fact that computational methods are again somehow behind the reality of drug development. We have unfortunately not been able to establish a valid model of protein-protein interaction and from that an idйe how to replace peptidic and proteinic drugs by ?nice? Lipinski-rule small molecules. Nobody has been able to predict one of the most exciting new drugs, pimecrolimus, a tacrolimus analogue. Ion channels and GCPRs very probably have multiple ligand interactions simultaneously.What is the contribution, hence, of atomic resolution to the design of a drug?