The Formulaire of 1821: Magendie and the First Pure Medicines

In 1821 a thin book appeared in Paris with a long title: Formulaire pour la préparation et l’emploi de plusieurs nouveaux médicamens — a handbook for preparing and using several new medicines. Its author, the physiologist François Magendie (1783–1855), was not offering new herbs or new mixtures. He was offering something medicine had never had before: a short list of pure chemical substances drawn out of plants — strychnine from nux vomica, morphine from opium, emetine from ipecacuanha root, quinine from cinchona bark — each one first tested on animals in his own laboratory. Historians of pharmacy describe it as the first formulary devoted to the newly isolated alkaloids, and they credit Magendie with standardising animal tests of each substance’s activity and safety.

This page tells the story of how that book came about. It starts in April 1809, when Magendie and the botanist-physician Alire Raffeneau-Delile reported that a Javanese arrow poison and two bitter seeds of the Strychnos family all acted on the same place in the body — the spinal cord — and it follows the idea that grew from that finding: that a plant drug works because of a chemical “principle” inside it, which chemists ought to be able to isolate. The plants themselves have their own page, Strychnos, Ipecac and the Plants Behind Magendie’s Medicines. Everything here is history and pharmacology; the doses and preparations printed in the Formulaire are deliberately not reproduced.

Table of Contents

  1. 1. Medicine Before Pure Drugs
  2. 2. Upas, Nux Vomica and Saint-Ignatius Bean, 1809
  3. 3. A Poison That Acts on the Spinal Cord
  4. 4. Predicting Strychnine
  5. 5. Emetine from Ipecac with Pelletier, 1817
  6. 6. How Poisons Reach Their Target
  7. 7. The Formulaire of 1821
  8. 8. ‘The Same in Man and in Animals’: The 1822 Preface
  9. 9. Nine Editions and a Growing List of Medicines
  10. 10. A Blueprint for Testing New Drugs
  11. Key Research Papers
  12. Connections
  13. Featured Videos

1. Medicine Before Pure Drugs

At the start of the nineteenth century a physician’s medicines came almost entirely from whole natural materials: dried roots, barks, seeds, leaves and resins, along with a handful of minerals. They were given as powders, infusions, tinctures and extracts. The trouble with a crude plant drug is that nobody knows exactly how much of the active substance a given spoonful contains. The amount varies with the species and variety of the plant, where and when it was gathered, how it was dried and stored, and how it was prepared. Two batches of the same bark could behave very differently in two patients.

Ideas about how drugs worked were just as uncertain: where in the body a medicine acted, and how it got there, were open questions. The historian M. P. Earles surveyed the competing answers of the period in a 1961 study of early theories of the mode of action of drugs and poisons.

Two changes arrived at almost the same moment. Chemists began to pull crystalline substances out of plant drugs — the German pharmacist Friedrich Sertürner obtained morphine from opium around 1804, first reported it in 1805 and named it in 1817 — and a young Paris physician began to test plant poisons on animals one question at a time. François Magendie had already announced, in a critical essay of 1809 sometimes called his “manifesto”, that most physiological “facts” had to be checked again by new experiments. The experiments on poisons that he began the same year are where historians place the start of experimental pharmacology.

Back to Table of Contents

2. Upas, Nux Vomica and Saint-Ignatius Bean, 1809

On 14 April 1809 Magendie read a memoir to the First Class of the Institut de France titled Examen de l’action de quelques végétaux sur la moelle épinière — “an examination of the action of some plants on the spinal cord”. The work had been done together with Alire Raffeneau-Delile (1778–1850), a botanist and physician. It was printed the same year in the Nouveau bulletin scientifique de la Société philomatique.

The starting point was upas, a famous arrow poison from Java. Delile’s own medical thesis of 1809 was devoted to it: Sur les effets d’un poison de Java appelé l’upas tieuté, et sur les différentes espèces de strychnos. Upas tieuté was prepared from a Strychnos plant. (The name “upas” was also used for a quite different Javanese poison, upas antiar, from the tree Antiaris toxicaria; the two are easily confused.)

Looking back in the 1822 edition of his Formulaire, Magendie explained what happened next. Upas could not be bought in commerce, so the two men looked for ordinary drugs with the same effects — and found them in two bitter seeds already sold by druggists: nux vomica, the seed of Strychnos nux-vomica, and the Saint-Ignatius bean, the seed of Strychnos ignatii. Three materials from different places and different plants turned out to produce the same violent effect in animals.

That comparison is the point historians stress. In the Dictionary of Scientific Biography, the historian of medicine Mirko Grmek describes these experiments as marking the beginning of modern pharmacology, because they were the first experimental comparison of similar effects produced by drugs of different botanical origin. As J. M. S. Pearce has summarised it, the similar effects depended on the drugs’ chemistry, not on the plant they came from.

Back to Table of Contents

3. A Poison That Acts on the Spinal Cord

All three materials caused the same picture in the animals: sudden, powerful convulsions with the body thrown into rigid spasm. The question Magendie and Delile asked was where in the body this action took place. Was it the brain, the nerves, the muscles, or something in between?

Their answer came from a simple and decisive kind of experiment. When the spinal cord was cut through below the brain — separating it from the brain — the poison still produced its convulsions in the body below the cut. When the spinal cord itself was destroyed, the convulsions stopped. The action, they concluded, lay in the spinal cord.

In the 1822 Formulaire Magendie put the result in a single sentence: the 1809 work had shown “qu’une famille entière de végétaux (les strychnos amers) a la propriété singulière d’exciter fortement la moelle épinière sans intéresser, autrement que d’une manière indirecte, les fonctions du cerveau” — that a whole family of plants, the bitter Strychnos species, has the singular property of strongly exciting the spinal cord without affecting the functions of the brain except indirectly.

Modern pharmacology has confirmed the location and explained the mechanism. In 1973 Anne Young and Solomon Snyder showed that radioactively labelled strychnine binds to the synaptic membranes of the spinal cord at the glycine receptor. Glycine is the main “brake” signal on the motor nerve cells of the spinal cord; strychnine blocks that brake, so the slightest stimulus sets off uncontrolled muscle contraction. Magendie’s 1809 finding and the 1973 receptor study describe the same event 164 years apart. The receptor story is told more fully on the plants and alkaloids page.

Back to Table of Contents

4. Predicting Strychnine

If three different plant materials share the same effect, the simplest explanation is that they share the same active substance. Magendie drew exactly that conclusion. According to Grmek, he held that the toxic or medicinal action of a natural drug depends on particular chemical substances in it, and that these substances ought to be obtainable in a pure state. As early as 1809 he suspected that the strychnos seeds contained such a substance — one that had not yet been found.

The chemists caught up within a decade. In 1818 the Paris pharmacists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou extracted a new crystalline vegetable alkali from the Saint-Ignatius bean and nux vomica and named it strychnine; their memoir was printed in 1819. In 1819 they also described brucine, a related alkaloid, from a bark later shown to come from Strychnos nux-vomica. The prediction made from animal experiments had been fulfilled by chemistry.

Pelletier and Caventou spelled out the same logic in their own words when they argued that a pure alkali carries the action of its plant: morphine represents the calming action of opium, and strychnine produces a terrible tetanus. Their next great isolation — quinine from cinchona bark, in 1820 — is described in the Pelletier and Caventou wing.

Here the two halves of early pharmacology met. The chemists supplied pure substances; the physiologist supplied a way of finding out, in living animals, what each substance actually did and where.

Back to Table of Contents

5. Emetine from Ipecac with Pelletier, 1817

Magendie did not only wait for chemists to confirm his ideas; he worked with them directly. His interest in vomiting went back to a Mémoire sur le vomissement of 1813 and to experiments on the effects of emetic drugs in humans and animals. The obvious next target was ipecacuanha, the South American root that druggists sold as an emetic.

Working with Pierre-Joseph Pelletier — with Pelletier alone, not Caventou, as some summaries have it — Magendie isolated the substance responsible for the root’s action and named it emetine. The joint Mémoire sur l’émétine et sur les trois espèces d’ipécacuanha was presented to the Académie des sciences on 25 February 1817. As its title shows, the memoir examined three different kinds of ipecacuanha root.

The emetine study was a model of what Magendie wanted pharmacology to be: chemistry and physiology in the same paper, the active principle of a familiar plant drug isolated and then tested on animals to show that it really was the active principle. Emetine went on to a long second career; nearly a century later the British physician Leonard Rogers reported in 1912 on injections of soluble emetine salts in amoebic dysentery, a story told on the plants page, along with emetine’s documented toxicity.

Back to Table of Contents

6. How Poisons Reach Their Target

Knowing where a poison acts raises a second question: how does it get there? In Magendie’s day a common view held that substances taken into the body were absorbed mainly through the lymphatic vessels. Magendie set out to test this.

Grmek describes the design. Magendie prepared an animal’s limb so that it was joined to the rest of the body only by an artery and a vein — and in some experiments not even by the vessels themselves, but by quills put in their place. A poison applied to that limb still acted on the whole animal. Since no lymphatic vessels and no nerves connected the limb to the body, the poison must have travelled in the blood. Magendie concluded that poisons are absorbed through the blood vessels and not only through the lymphatics.

From this came what Grmek calls his principle of local action: a substance acts by coming into direct contact with the organ it affects, carried there by the blood. Today that idea is so basic — a drug must reach its receptor — that it is easy to forget it once had to be proved.

The historian José Ramón Bertomeu-Sánchez has examined this work alongside that of the toxicologist Mateu Orfila, who was teaching in Paris at the same time. In a 2012 study he traced how their animal experiments on the absorption of poisons, their debates over “vital forces”, and the practical needs of poisoning trials in French courtrooms fed into one another. The same experiments that told a physician how a medicine reached its target told a forensic expert where to look for a poison after death.

Back to Table of Contents

7. The Formulaire of 1821

By 1821 the pieces were in place. Morphine, strychnine, brucine, emetine, quinine and cinchonine had been isolated, most of them by Paris pharmacists, and Magendie had spent more than ten years testing plant poisons on animals and at the bedside. That year — the same year he founded the Journal de physiologie expérimentale and was elected to the Académie des sciences — he published the Formulaire.

It was a practical handbook, not a treatise. For each new substance it described what it was, where it came from, how it was prepared in the pharmacy, what Magendie had found in animal experiments, how it acted in patients as far as he had observed, and how it was prescribed. According to the historians Alain Ségal and François Trépardoux, who studied the whole series of Formulaires, the first issue was devoted chiefly to the pure alkaloids — strychnine, quinine and morphine — together with a few mineral chemicals such as the hydrocyanates (salts of prussic acid), iodine and, in later issues, bromide, all resting on the chemical work of Pelletier, Caventou and their colleagues.

Some later accounts give a different date or a longer list. J. M. S. Pearce, writing in Hektoen International, dates the Formulaire to 1827, but that is a later edition; the first appeared in 1821. Grmek’s list of the alkaloids the book introduced includes codeine, but codeine was only isolated in 1832, so it belongs to the later editions, not the first.

The Formulaire’s novelty was its premise. Earlier pharmacopoeias collected whole plants and compound mixtures handed down by tradition. Magendie’s book collected single chemical substances whose action had been established by experiment. It was, in effect, the first prescribing guide of the age of pure drugs.

Back to Table of Contents

8. ‘The Same in Man and in Animals’: The 1822 Preface

The second edition, “revue et augmentée” (revised and enlarged), appeared in 1822 from the Paris publisher Méquignon-Marvis, a slim volume of about ninety pages. Its title page lists what it covers: la noix vomique, la morphine, l’acide prussique, la strychnine, la vératrine, les alcalis des quinquinas, l’émétine, l’iode — nux vomica, morphine, prussic acid, strychnine, veratrine, the cinchona alkaloids, emetine and iodine. Inside are chapters on the resinous extract of nux vomica, strychnine, morphine and its salts, narcotine (the “matière de Derosne” from opium), emetine, the cinchona alkaloids cinchonine and quinine, veratrine, prussic acid, solanine, delphine, “gentianin” from gentian root, and iodine.

The preface is where Magendie set out his reasoning, and it reads today like a statement of method.

Animals and humans respond alike

Ten years of experiments in his laboratory and at the bedside, he wrote, allowed him to state “que la manière d’agir des médicamens et des poisons est la même sur l’homme et sur les animaux” — that medicines and poisons act in the same way on humans and on animals. That claim is the foundation of every animal study that precedes a human trial.

Pure substances have a fixed strength

The new substances, he explained, act in very small amounts; they are not mixed with other materials that can mask or alter their action; and because their chemical nature and their method of preparation are fixed, “on n’a point à craindre de variation dans leur force” — there is no need to fear variation in their strength. This was the decisive advantage over the crude drugs described in section 1.

Testing on himself

Magendie added that he was so confident of the animal-to-human principle that he did not hesitate to try on himself substances he had found harmless in animals (“je n’hésite point à essayer sur moi-même les substances que j’ai reconnues innocentes sur les animaux”). Self-experimentation was common among the physicians and pharmacists of the time — Sertürner had tested morphine on himself — and it is reported here as part of the historical record of how drugs were first assessed.

Time as the judge

Magendie did not claim the last word. Only time, he wrote, would show the true advantages and drawbacks of the new medicines. In the same edition he credited the Paris physician Pierre Fouquier with publishing cases of paralysis treated with nux vomica before him, and reported that he had obtained similar results; that is his own clinical account, preserved as history.

Back to Table of Contents

9. Nine Editions and a Growing List of Medicines

The Formulaire was a success. Ségal and Trépardoux count nine consecutive issues between 1821 and 1836, and their study follows the series to 1840. Each edition grew as new substances came out of the laboratories of Paris and elsewhere.

The title pages trace the growth. The 1829 edition adds, among others, quinine sulphate and cinchonine, bromine, mercury iodide, potassium cyanide, croton oil, salts of gold and platinum, chlorine and the chlorides, the bicarbonates, the bark of pomegranate root and phosphorus. By the 1835 and 1836 editions the title also names codeine (isolated from opium in 1832), “hydrocyanic ether” and salicine — the bitter glycoside from willow bark that later chemists would turn into salicylic acid and, eventually, aspirin.

Quinine, one of the cinchona alkaloids in the Formulaire from its first issue, was the purified form of the bark long used against intermittent fevers — the fevers now known as malaria. The history of malaria traces how quinine came to dominate fever treatment in the decades that followed.

By the late 1830s the range of the book had moved well beyond the strychnos poisons with which Magendie had begun. What stayed constant was the format: one chemically defined substance per chapter, its origin, its preparation and the animal and clinical observations behind its use.

Back to Table of Contents

10. A Blueprint for Testing New Drugs

Ségal and Trépardoux make the larger claim directly. In their 2015 study of the Formulaires, they argue that Magendie standardised the testing of each new substance on animals for both activity and safety before describing its use in patients, and that in doing so he anticipated the kind of evaluation that twentieth-century drug-registration rules came to require. The sequence he followed — a pure, defined substance; experiments in animals to find what it does and where; cautious observation in humans; publication — is recognisably the sequence a new medicine passes through today.

Other historians place him at the same starting line. The historian Paul Mazliak, writing in 2013, called him the creator of pharmacology and the inspirer of Claude Bernard’s researches. The neuroscience historians R. Shane Tubbs and colleagues, in a 2008 review, listed pharmacology alongside neuroanatomy and physiology among the fields he shaped, and Frank Stahnisch’s 2009 biographical note in the Journal of Neurology gives a short modern summary of his career.

The work had its limits and its costs. Magendie’s experiments were performed on living animals without anaesthesia, which was not yet available, and his public demonstrations later drew strong protest; that controversy is described on the legacy page. The drugs themselves were often dangerous: strychnine, prussic acid and emetine are potent poisons, and the line between medicine and poison that the Formulaire tried to fix with exact chemistry remained narrow. Strychnine’s later career as a nineteenth-century “tonic” is the subject of John Haller’s 1973 history of strychnine in the materia medica of that century.

Magendie’s most direct heir was his own assistant and successor at the Collège de France, Claude Bernard, who took the same approach to the arrow poison curare and showed exactly where in the body it acts. The line from the strychnos experiments of 1809, through the Formulaire, to Bernard’s curare studies and on to the receptor pharmacology of the twentieth century is one continuous idea: a drug is a chemical, and its action can be found by experiment.

Back to Table of Contents

Key Research Papers

  1. Ségal A, Trépardoux F. [The Formulaires of Magendie (1821-1840) of the chemical pharmacy to pharmacology]. Hist Sci Med. 2015;49(2):141-56. PubMed PMID: 26492670
  2. Bertomeu-Sánchez JR. Animal experiments, vital forces and courtrooms: Mateu Orfila, François Magendie and the study of poisons in nineteenth-century France. Ann Sci. 2012;69(1):1-26. PubMed PMID: 22530381
  3. Earles MP. Early theories of the mode of action of drugs and poisons. Annals of Science. 1961;17(2):97-110. DOI: 10.1080/00033796100202571
  4. Mazliak P. [Medical recollections. François Magendie, creator of the pharmacology, inspirer of Claude Bernard’s researches]. Rev Prat. 2013;63(7):1030-3. PubMed PMID: 24167908
  5. Albury WR. Physiological explanation in Magendie’s manifesto of 1809. Bull Hist Med. 1974;48(1):90-9. PubMed PMID: 4608397
  6. Young AB, Snyder SH. Strychnine binding associated with glycine receptors of the central nervous system. Proc Natl Acad Sci U S A. 1973;70(10):2832-6. PubMed PMID: 4200724
  7. Haller JS Jr. The history of strychnine in the nineteenth-century materia medica. Trans Stud Coll Physicians Phila. 1973;40(4):226-38. PubMed PMID: 4574625
  8. Tubbs RS, Loukas M, Shoja MM, Shokouhi G, Oakes WJ. François Magendie (1783-1855) and his contributions to the foundations of neuroscience and neurosurgery. J Neurosurg. 2008;108(5):1038-42. PubMed PMID: 18447728
  9. Stahnisch FW. François Magendie (1783-1855). J Neurol. 2009;256(11):1950-2. PubMed PMID: 19693629
  10. Park C. An Experimentalist Who Shunned Hypotheses? A Study of François Magendie’s Experimental Medicine. Uisahak. 2025;34(1):279-314. PubMed PMID: 40443274
  11. Rogers L. The rapid cure of amoebic dysentery and hepatitis by hypodermic injections of soluble salts of emetine. Br Med J. 1912;1(2686):1424-5. PubMed PMID: 20766221

PubMed Topic Searches

  1. Magendie Formulaire
  2. Magendie history
  3. Strychnine history
  4. Emetine and ipecacuanha

Further Reading

Back to Table of Contents

Connections

Back to Table of Contents