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Medicines by Design We would like your comments on Medicines By Design. Please give us your opinion by filling out this postage-paid response card. Join our Findings mailing list. For sample issues, see http://publications.nigms.nih.gov/findings. 1. Extent to which the publication held your interest q I would like to receive Findings, a magazine that profiles two NIGMS-supported scientists, features brief descriptions of recent clinically relevant 2. Understandability research, and includes a crossword puzzle based on words used in the articles. 3. Amount and type of information presented q I would like to receive a free CD-ROM containing NIGMS science education booklets on topics such as cell biology, chemistry, genetics, pharmacology, and structural biology. These booklets are geared toward 4. Usefulness and value of such a publication a high school and early college audience. Print Medicines By Design copies of the publications can be ordered from READERS http://www.nigms.nih.gov/publications/classroom Please comment on whether Medicines By Design helped you learn more about: Name 1. Pharmacology research Address U.S. DEPARTMENT OF 2. What it’s like to be a scientist City HEALTH AND HUMAN SERVICES National Institutes of Health State Zip Code National Institute of General Medical Sciences 3. The excitement of biomedical research today E-mail (optional) U.S. DEPARTMENT OF NIH Publication No. 06-474 HEALTH AND HUMAN SERVICES Phone (optional) Reprinted July 2006 National Institutes of Health http://www.nigms.nih.gov National Institute of General Medical Sciences TTENTION Other Comments: A What Is NIGMS? Discrimination Prohibited Accessibility The National Institute of General Medical Sciences Under provisions of applicable public laws enacted This publication can be made available in (NIGMS) supports basic biomedical research on by Congress since 1964, no person in the United formats that are more accessible to people genes, proteins, and cells. It also funds studies on States shall, on the grounds of race, color, national with disabilities. To request this material in a fundamental processes such as how cells commu- origin, handicap, or age, be excluded from partici- different format, contact the NIGMS Office nicate, how our bodies use energy, and how we pation in, be denied the benefits of, or be subjected of Communications and Public Liaison at respond to medicines. The results of this research to discrimination under any program or activity 301-496-7301, TDD 301-402-6327; send e-mail increase our understanding of life and lay the (or, on the basis of sex, with respect to any educa- to [email protected]; or write to the office at foundation for advances in the diagnosis, treatment, tion program or activity) receiving Federal financial the following address: 45 Center Drive MSC and prevention of disease. The Institute’s research assistance. In addition, Executive Order 11141 6200, Bethesda, MD 20892-6200. If you have training programs produce the next generation of prohibits discrimination on the basis of age by questions about this publication, you can use biomedical scientists, and NIGMS has programs to contractors and subcontractors in the performance the same contact information to reach the writer, DEPT OF HEALTH AND HUMAN SERVICES encourage minorities underrepresented in biomedical of Federal contracts, and Executive Order 11246 Alison Davis, Ph.D. NATIONAL INSTITUTES OF HEALTH NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES and behavioral science to pursue research careers. states that no federally funded contractor may 45 CENTER DR RM 3AN.32 MSC 6200 Additional Copies BETHESDA MD 20892-6200 NIGMS supported the research of most of the discriminate against any employee or applicant and Web Links OFFICIAL BUSINESS scientists mentioned in this booklet. for employment because of race, color, religion, PENALTY FOR PRIVATE USE $300 To order additional copies of Medicines By Design sex, or national origin. Therefore, the programs of Disclaimer or other free publications available from the National Institute of General Medical Sciences NIGMS, go to http://publications.nigms.nih.gov/ Trade names have been used throughout this must be operated in compliance with these laws order/classroom.htm or use the contact booklet to illustrate concepts about medicines and Executive Orders. information above. that are familiar to readers. The mention of specific products is not an endorsement of their NATIONAL INSTITUTES OF HEALTH Medicines By Design is available online at NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES use or effectiveness. OFFICE OF COMMUNICATIONS AND PUBLIC LIAISON http://publications.nigms.nih.gov/medbydesign. 45 CENTER DR RM 3AN.32 MSC 6200 BETHESDA MD 20814-9692 Medicines By Design U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NIH Publication No. 06-474 National Institutes of Health Reprinted July 2006 National Institute of General Medical Sciences http://www.nigms.nih.gov Written by Alison Davis, Ph.D., under contracts 263-MD-205019 and 263-MD-212730. Produced by the Office of Communications and Public Liaison National Institute of General Medical Sciences National Institutes of Health U.S. Department of Health and Human Services Contents FOREWORD: A VISIT TO THE DOCTOR 2 CHAPTER 1: ABCS OF PHARMACOLOGY 4 A Drug’s Life 5 Perfect Timing 9 Fitting In 10 Bench to Bedside: Clinical Pharmacology 13 Pump It Up 14 CHAPTER 2: BODY, HEAL THYSELF 16 The Body Machine 16 River of Life 18 No Pain, Your Gain 20 Our Immune Army 23 A Closer Look 26 CHAPTER 3: DRUGS FROM NATURE, THEN AND NOW 28 Nature’s Medicine Cabinet 28 Ocean Medicines 30 Tweaking Nature 33 Is It Chemistry or Genetics? 34 Testing…I, II, III 36 CHAPTER 4: MOLECULES TO MEDICINES 38 Medicine Hunting 38 21st-Century Science 40 Rush Delivery 41 Transportation Dilemmas 43 Act Like a Membrane 44 The G Switch 46 MEDICINES FOR THE FUTURE 48 GLOSSARY 50 Foreword: A Visit to the Doctor May 17, 2050—You wake up feeling terrible, That’s right, your DNA. Researchers predict that the medicines of the future may not only look and and you know it’s time to see a doctor. work differently than those you take today, but In the office, the physician looks you over, tomorrow’s medicines will be tailored to your genes. In 10 to 20 years, many scientists expect listens to your symptoms, and prescribes that genetics —the study of how genes influence actions, appearance, and health—will pervade a drug. But first, the doctor takes a look medical treatment. Today, doctors usually give you at your DNA. an “average” dose of a medicine based on your body size and age. In contrast, future medicines may match the chemical needs of your body, as influenced by your genes. Knowing your unique genetic make-up could help your doctor prescribe the right medicine in the right amount, to boost its effectiveness and minimize possible side effects. Along with these so-called pharmacogenetic approaches, many other research directions will help guide the prescribing of medicines. The science of pharmacology—understanding the basics of how our bodies react to medicines and how medicines affect our bodies—is already a vital part of 21st-century research. Chapter 1, “ABCs of Pharmacology,” tracks a medicine’s journey through the body and describes different avenues of pharmacology research today. Medicines By Design I Foreword 3 Stay tuned for changes in the way you take delivery, discussed in Chapter 4, “Molecules to medicines and in how medicines are discovered Medicines,” is advancing progress by helping get and produced. In Chapter 2,“Body, Heal Thyself,” drugs to diseased sites and away from healthy cells. learn how new knowledge about the body’s own Medicines By Design aims to explain how molecular machinery is pointing to new drugs. As scientists unravel the many different ways medicines scientists understand precisely how cells interact in work in the body and how this information guides the body, they can tailor medicines to patch gaps the hunt for drugs of the future. Pharmacology in cell communication pathways or halt signaling is a broad discipline encompassing every aspect circuits that are stuck “on,” as in cancer. of the study of drugs, including their discovery Scientists are developing methods to have and development and the testing of their action animals and plants manufacture custom-made in the body. Much of the most promising medicines and vaccines. Experimental chickens pharmacological research going on at universities are laying medicine-containing eggs. Researchers across the country is sponsored by the National are engineering tobacco plants to produce new Institute of General Medical Sciences (NIGMS), cancer treatments. Topics in Chapter 3, “Drugs a component of the National Institutes of Health From Nature, Then and Now,” will bring you up (NIH), U.S. Department of Health and Human to speed on how scientists are looking to nature Services. Working at the crossroads of chemistry, for a treasure trove of information and resources genetics, cell biology, physiology, and engineering, to manufacture drugs. pharmacologists are fighting disease in the laboratory Advances in understanding the roots of disease and at the bedside. are leading to new ways to package tomorrow’s medicines. Along with biology and chemistry, the engineering and computer sciences are leading us to novel ways of getting drugs where they need to go in the body. Cutting-edge research in drug CHAPTER 1 ABCs of Pharmacology now why some people’s stomachs burn after medicines affect the body. Pharmacology is often K they swallow an aspirin tablet? Or why a confused with pharmacy, a separate discipline in swig of grapefruit juice with breakfast can raise the health sciences that deals with preparing and blood levels of some medicines in certain people? dispensing medicines. Understanding some of the basics of the science For thousands of years, people have looked in of pharmacology will help answer these questions, nature to find chemicals to treat their symptoms.
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