As long as humans and their animals have suffered from disease, chemical substances have played a role in their treatment. Substances obtained from plants and animals or their products were used according to precise prescriptions through antiquity. The mechanism attributed to why these substances were effective are deeply rooted in the beliefs and mythologies of each culture, as were the rituals involved in their preparation.

The early history of pharmacology parallels human efforts to compile records of ailments and their remedies. The earliest recorded compilation of drugs, the Pen Tsao, consisted of a list of herbal remedies compiled in the reign of Chinese Emperor Shennung in 2700 B.C. Classic examples of medicinal use of chemicals, herbs, and other natural substances are found in the recorded papyri of ancient Egypt. The Kahun Papyrus, written about 2000 B.C., lists prescriptions for treating uterine disease in women and specifically addresses veterinary medical concerns. The Ebers Papyrus, written in 1150 B.C. is a collection of folklore covering 15 centuries of history. It is composed of over 800 prescriptions for salves, plasters, pills, suppositories, and other dosage forms used to treat specific ailments.

The ancient Greek philosopher–physicians of 500 B.C. taught that health was maintained by a balance of “humors,” which were affected by temperature, humidity, acidity, and sweetness, rather than to the direct actions of gods or demons. Disease was treated by returning these humors to a proper balance. Hippocrates (460–370 B.C.) was an ancient Greek physician of the Age of Pericles. He is referred to as the “father of medicine” in recognition of his lasting contributions to the field as the founder of the Hippocratic school of medicine. He was a firm believer in the healing powers of nature, conducted systematic observations of his patients’ symptoms, and began moving the practice of medicine from an art to a systematic clinical science. The first true material medica, a compilation of therapeutic substances and their uses, was compiled in 77 A.D. by Aristotle’s student Dioscorides, while serving as a surgeon in Nero’s Roman Legion traveling throughout the Mediterranean. This served as the basis for the later works of Galen (131–201) that emerged as the authoritative material medica for the next 1,400 years! In fact, some pharmaceutical preparations consisting of primarily herbal or vegetable matter are still referred to as galenical preparations. As the Dark Ages descended upon Europe, such scholarship transferred to Byzantium, where in fact a veterinary compilation for farm animal treatments, Publius Vegetius, was compiled in the fifth century.

It took until the Renaissance to awaken the spirit of discovery in Europe. The Swiss physician Theophrastus Bombastus von Hohenheim (1492–1541), known as Paracelsus, introduced the clinical use of laudanum (opium) and a number of tinctures (extracts) of various plants, some of which are still in use today. He is remembered for using drugs for specific and directed purposes, and for the famous dictum “All substances are poisons; there is none which is not a poison. The proper dose separates a poison from a remedy.” As these practices took root, official compilations of medicinal substances, their preparation, use, and dosages, started to appear in Europe. These publications, termed pharmacopeia, provided a unifying framework upon which the pharmaceutical sciences emerged. The first printed pharmacopeia, titled the Dispensatorium, was published by Valerius Cordus in 1547 in Nuremberg, Germany. Local publications emerged in different European cities, with two pharmacopeias published in London in 1618. The Edinburgh Pharmacopoeia published in 1689 became the most influential during this period. It took until the mid-19th century before truly national pharmacopeias took hold, with the first United States Pharmacopeia published in 1820. The first United States Pharmacopeia has been given the title USP-0; the current edition of the United States Pharmacopeia is titled USP-39 and the National Formulary titled NF 34, which includes excipients. There was also a British pharmacopeia first published in 1864 and the British Pharmacopeia continues to be published today.

The history of pharmacology parallels the development of modern medicine and the realization that specific natural products and substances may cure specific diseases. The 16th and 17th centuries were marked by great explorations and the beginning of medical experimentation. In 1656, Sir Christopher Wren made the first intravenous injection of opium in a dog. The bark of the cinchona tree was brought by Jesuits from South America for use of treatment of malaria. In 1783, the English physician William Withering reported on his experience in the use of extracts from the foxglove plant to treat patients with “dropsy,” a form of edema most likely caused by congestive heart failure.

In the early 1800s the French physiologist–pharmacologist Megendie, working with the pharmacist Pelletier, studied the effects of intravenous injections of ipecac, morphine, strychnine, and other substances on animals. Megendie was the first to prove that chemicals can be absorbed into the vascular system to exert a systemic effect. A prolific scientist, he also published a formulary that survived through eight editions from 1821 to 1836. The Spanish physician Orfila published the results of many experiments in a book entitled Toxicologie Generale in 1813. A student of Megendie, the famous physiologist Claude Bernard, and others, showed in the mid-1800s that the active ingredient of foxglove botanical preparations was digitalis, and its action was on the heart. We continue to use digoxin today for the treatment of congestive heart failure in humans and animals. The important aspect of these early studies was that they used the experimental paradigm for demonstrating chemical activity, establishing both the philosophy and methods upon which the discipline of modern pharmacology is based.

The term Pharmakologie was applied to the study of material medica by Dale in London as early as 1692; however, it is generally regarded that the biochemist Rudolph Buchheim in the Baltic city of Dorpat established the first true experimental laboratory dedicated to pharmacology in the mid-18th century. He published some 118 contributions on a variety of drugs and their actions, and argued for pharmacology to be a separate discipline distinct from material medica, pharmacy, and chemistry. His work included in 1849 a textbook Beiträge zur Ärzneimittellehre, which classified drugs based on their pharmacological action in living tissue. He deleted traditional remedies if he could not demonstrate their action in his laboratory. This is the beginning of what we now know as evidence-based pharmacology, which requires that a chemical be termed a drug only if a specific action in living tissues can be demonstrated.