Although surprising, it seems fitting that a drug developed at the dawn of the era of rational drug design and therapeutics, methotrexate, should remain in common use for the therapy of so many different kinds of illnesses. Moreover, methotrexate has completely revolutionized the way in which medicine is practiced in a number of speciality areas. First developed to treat malignancies, methotrexate is now commonly used to treat gynecological problems, inflammatory arthritis, skin disease and probably other ailments as well. This work is designed to give a broad overview of the history of methotrexate's development, its prior use and its current therapeutic uses. As discussed in Chapter I, aminopterin and methotrexate were designed to inhibit mammalian folate metabolism but the concept of folic acid antag onism was soon applied to the development of antibacterial and anti parasitic agents. Trimethoprim and sulfa drugs were among the first antibiotics developed and they also remain quite useful today for the treat ment of a variety of infections.

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