RESUMO
Clinical pharmacology/research has a very interesting history. It started in the 40's of the 20th century through the pioneering work of Harry Gold at Cornell University, New York. Clinical research is an integral part of drug development. Drug development can be hastened by a number of new techniques with reduction in cost. In addition reverse pharmacology approaches for drug discovery have come to occupy a special place. 85% of the neutral antagonists act as inverse agonists. Inverse agonists have a distinct effect on receptor regulation as opposed to neutral antagonists. Orphan receptors constitute about 50% of the GPCRs. It is estimated that now there are nearly 175 orphan receptors after 125 having been deorphanised. Targeting these orphan receptors can lead to about the same number of ligands and antagonists thereof. Polymorphism of cytochrome P450 provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. It is estimated that such personalized P450 gene-based treatment would be relevant for 10- 20% of all drug therapy.