世界薬理学・毒物学ジャーナル

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Pharmacology in drug discovery

Editorial

Pharmacology, the science underlying the interaction between chemicals and living systems, emerged as a definite discipline allied to medicine within the mid-19th century, when the essential principles of physiology and chemistry provided a framework for understanding how therapeutic drugs act. As a discipline, it grew out of the necessity to know and improve therapeutics, and this remains its main focus. Rational drug design, supported pharmacological principles, began within the early 20th century, and accelerated rapidly from the mid20th century onwards, with essential contributions from pharmacologists. The majority of currently used drugs, which have steadily transformed practice, have come from applying pharmacological thinking to the drug discovery process. Life-changing innovations include antihypertensive drugs, antibiotics, antiviral drugs, antipsychotic drugs, surgical anaesthetics and oral contraceptives. Illnesses that were previously untreatable are now routinely and successfully treated. These interactions are reciprocal: the living organism affects the drug or medicine, and therefore the drug or medicine affects the organism. In some instances, notably antimicrobial drugs, quite one biological organism is affected. Pharmacology aims to elucidate the mechanisms that underlie these interactions, and is therefore intrinsically reductionist; it aims to seek out underlying principles, not only to collate isolated facts. The pharmacologist can chose to review the interactions between living organisms and medicines or medicines at any level of integration and using any methodology available. Nevertheless, the understanding of interactions between medicines and therefore the most complex Pharmacology in drug discovery of systems - the intact being - is that the ultimate goal. Of course, this also perfectly describes the method of drug discovery. The human genome and its ramifications are providing much new information about disease mechanisms and possible new therapeutic approaches, providing the idea for brand spanking new drug discovery projects - presaging a second revolution within the view of the many biomedical scientists - during which pharmacologists will play an important role. What matters to the individual patient is that the beneficial effect of the drug on symptoms, disabilities and survival, balanced against its unwanted effects. The pharmacologist must understand drug action across all levels of biological organisation, from the molecules (drug targets) with which drug molecules interact chemically, through the cellular and physiological effects that this interaction produces, and therefore the way during which these effects influence the disease process, culminating with the expected impact on patient care. Both basic and clinical pharmacologists play an important role in any drug discovery team