tailieunhanh - CLINICAL PHARMACOLOGY 2003 (PART 5)

Preclinical drug development. Discovery of new drugs in the laboratory is an exercise in prediction • Techniques of discovery. Sophisticated molecular modelling allows precise design of potential new therapeutic substances and new technologies have increased the rate of development of potential medicines. Studies in animals and in humans Prediction. Failures of prediction occur and a drug may be abandoned at any stage, including after marketing. New drug development is a colossally expensive and commercially driven activity. . | 3 SECTION I Discovery and development of drugs SYNOPSIS Preclinical drug development. Discovery of new drugs in the laboratory is an exercise in prediction Techniques of discovery. Sophisticated molecular modelling allows precise design of potential new therapeutic substances and new technologies have increased the rate of development of potential medicines. Studies in animals and in humans Prediction. Failures of prediction occur and a drug may be abandoned at any stage including after marketing. New drug development is a colossally expensive and commercially driven activity. Orphan drugs and diseases. Preclinical drug development Pharmacology and medicinal chemistry have transformed medicine from an intellectual exercise in diagnosis into a powerful force for the relief of human disease CT Dollery 1994 The development of new medicines drugs is an exercise in prediction from laboratory studies in vitro and in vivo animals which forecast what the agent will do to man. Medicinal therapeutics rests on the two great supporting pillars of pharmacology Selectivity the desired effect alone is obtained We must learn to aim learn to aim with chemical substances Paul Ehrlich .1 2 Dose . .The dose alone decides that something is no poison Paracelsus .3 For decades the rational discovery of new medicines has depended on modifications of the molecular structures of increasing numbers of known natural chemical mediators. Often the exact molecular basis of drug action is unknown and this book contains frequent examples of old drugs whose 1 In this chapter we are grateful for permission from Professor Sir Colin Dollery to quote directly and indirectly from his Harveian Oration Medicine and the pharmacological revolution 1994 Journal of the Royal College of Physicians of London 28 59-69. 2 Paul Ehrlich 1845-1915 German scientist who pioneered the scientific approach to drug discovery. The 606th organic arsenical that he tested against spirochaetes in animals became a successful .