Drug Research: Yesterday, Today, and Tomorrow

The search for medicines is an old dream of mankind. It began with empirical observations of the uptake of natural products from food. The first prescriptions go back to the ancient Egyptians and traditional Chinese medicine. Paracelsus saw the human being as a “chemical laboratory” and founded scientific medical research. For the first time, the ingredients of medicines were held responsible for their healing effects, and with the advent of organic chemistry, the first therapeutic principles based on pure organic compounds became available. The great age of natural products from plants and their active ingredients began. Systematic animal studies began in the last century and can be considered the starting point for drug discovery. In vitro models are necessary for testing large series of potentially active compounds, but animal models are necessary for correlating data and predicting therapeutic effects in humans. Without the successful control of infectious diseases, our current life expectancy would not be possible. However, the best weapons against infectious diseases are becoming increasingly blunt due to the widespread use of antibiotics and the spread of resistant pathogens. Increasing resistance to available drugs is a global problem. Drug discovery has been greatly stimulated by the elucidation of biological concepts, pathways and regulatory cycles using endogenous compounds. Structural variations of neurotransmitters, hormones, steroids, or natural substrates have led to many developed drugs, and the establishment of in vitro models, which replaced biological animal testing with test tube assays, marked the beginning of systematic compound testing. Genetic engineering made it possible to produce sufficient quantities of pure proteins for testing. The discovery of neuroleptics, antidepressants, anticonvulsants, and sedatives revolutionized the treatment of psychiatric disorders. Molecular modeling and computer-aided design, together with structural biology, provide access to rational considerations of drug action. The first structure-based design project was performed on hemoglobin, and the first drug developed using a structure-based approach was the antihypertensive drug captopril. Today, the evaluation of drug efficacy and safety has reached an extraordinarily high level. The global pharmaceutical market is large and highly competitive. Annual sales are approaching 1.45 billion USD. Only a few drugs account for a large share of sales and determine the particular dynamics of the market, which has become smaller and smaller with fewer and fewer companies. Often, a single drug can make or break a company. Drugs remain at the center of public interest. It is no longer the physician alone who influences the prescription of drugs. Multiple sources of information influence and inform the patient. A proper risk-benefit analysis of a drug is required, taking into account not only the desired therapeutic effect but also the severity of the disease. https://sn.pub/vrehez