[How studies on curare contributed to the development of neurophysiological research in Brazil]. / Importance des études transnationales sur le curare dans le développement de la recherche en neurophysiologie au Brésil.

Curare is a poison obtained from different species of plants in South America, which was used in arrows by the natives. Its lethal paralyzing potential and mechanism of action began to be explored in the 19th century. In this article, we highlight the research on this poison and the fruitful exchanges between the Brazilian Emperor Dom Pedro II and the researchers João Baptista de Lacerda, Louis Couty and Alfred Vulpian who contributed to the development of experimental neurophysiology in Brazil. Vulpian found that curare does not affect the nerve itself, but acts between the nerves and the muscle, through a "ligand substance" - this Vulpian's pioneering concept is often wrongly attributed to Claude Bernard. These prestigious scientists contributed to the transnational circulation of knowledge that later yielded in the preparation of curare purified extract used for convulsive therapy and anesthesia.

Title: Importance des études transnationales sur le curare dans le développement de la recherche en neurophysiologie au Brésil. Abstract: Le curare, un poison obtenu à partir de différentes espèces de plantes en Amérique du Sud, était utilisé sur les flèches par les autochtones. Son potentiel paralysant mortel et son mécanisme d'action ont commencé à être explorés par les chercheurs au XIXe siècle. Dans cet article, nous rappelons l'historique des recherches sur ce poison et les échanges entre l'empereur brésilien Dom Pedro II et les chercheurs João Baptista de Lacerda, Louis Couty et Alfred Vulpian qui ont beaucoup contribué au développement scientifique brésilien. Vulpian a découvert que le curare n'affecte pas le nerf lui-même, mais agit entre celui-ci et le muscle, par l'intermédiaire d'une « substance de liaison ¼ ­ ce concept développé par Vulpian est souvent attribué à tort à Claude Bernard. Les travaux pionniers de ces savants prestigieux ont ultérieurement abouti à la préparation d'extrait purifié de curare, d'intérêt thérapeutique majeur pour le traitement de convulsions et pour l'anesthésie.

The history of acetylcholinesterase inhibitors in the treatment of myasthenia gravis.

The beneficial effects of acetylcholinesterase inhibitors for the treatment of myasthenia gravis (MG) was a major discovery that came about through one young physician putting together a string of previous observations. To understand how this discovery came to light, we must first go back to earlier times when men hunted by bow-and-arrow to capture their prey. The substance used to poison the prey was eventually was identified as curare. Centuries later, a connection was made between the physiological effects of curare and a disease entity with no known pathological mechanism or treatment, myasthenia gravis. In 1935, house officer Dr. Mary Walker was the first physician to try physostigmine in the treatment of MG, which had previously been used to treat curare poisoning. What she saw was a dramatic improvement in the symptoms experienced in patients with MG, and thus became the first documented case of use of physostigmine, an acetylcholinesterase inhibitor, in the treatment of MG. This article is a summary of the history of the use of acetylcholinesterase inhibitors in the treatment of myasthenia gravis. This article is part of the special issue entitled 'Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield'.

The Place of Erythroidines in the History of Neuromuscular Blockers.

Between 1938 and 1951 erythroidine derivatives were seriously considered as alternatives to curare for the provision of muscle relaxation. This has been overlooked in the published history of anaesthesia. The first publication on the paralysing effect of an extract of Erythrina americana was in 1877, but this was in a Mexican journal, which was not widely read. Sixty years later erythroidine was isolated, and in 1938 it was first used clinically to treat spastic dystonia, preceding the use of Intocostrin for this purpose. By 1943 dihydro-ß-erythroidine was prepared in crystalline form, which was equipotent with curarine and of acceptable duration; it was used in clinical anaesthesia in 1946. In the 1940s curare was presented in solutions with potency stated in units, determined by bioassay, which was a disadvantage compared with the straightforward mg of dihydro-ß-erythroidine. However, by the early 1950s, improvement in the pharmaceutical presentation of d-tubocurarine and new neuromuscular blockers, displaced the erythroidines.

Francis Sibson (1814-1876): the unsung hero of modern surgery and anesthesia.

Francis Sibson (1814-1876) was a British physician and anatomist widely regarded as a true pioneer of the medical profession. He overcame a tragic and difficult childhood to become an avid educator at several medical schools and dedicated his life to research. For modern scientists, he is most remembered for describing Sibson's fascia, his experimental use of curare in the treatment of hydrophobia and tetanus, and his detailed description of the positions and movements of internal organs. He died on September 7, 1876 at the age of 62 from complications of an aortic aneurysm.

[Claude Bernard and his successors on curare: epistemological questions at stake]. / Claude Bernard et ses suiveurs sur la question du curare : enjeux épistémologiques.

Long lasting polemics about the mechanisms of the action of curare took place at the Société de Biologie over thirty years. After a period during which poisoning protocols were developed on various animal species, where Claude Bernard, Vulpian and their colleagues were involved, German electrophysiology combined its results with new histological data about motor end-plates, elaborating a theory in which young physiologists fought against Claude Bernard's views and finally managed to convince him. According to the new theory proposed by Vulpian, curare blocked transmission between end-plate and muscle. This first draft of the neurotransmission theory helps us to understand the rise of a novel physiology in the context of the school of Claude Bernard with a better integration of disciplines and a more prominent faith in reductionism and materialism.

[Autopsy of a common error: the introduction of curare in Europe by W. Raleigh]. / Autopsie d'une erreur commune: l'introduction du curare en Europe par W. Raleigh.

One of the most erroneous and repeated assertion in the history of pharmacology for anaesthetists is to say that "the curare was introduced in Europe by Sir Walter Raleigh under the name of ourari". On the contrary, the names to be reminded are: Lawrence Keymis for the first citation of the word ourari, José Gumilla for the word curare and the description of its effects, Charles-Marie de La Condamine for the import of the first known samples. The mistake was initiated by Alexander von Humboldt and developed by the physiologist Münter, a student of Johannes Müller, quoted by Claude Bernard. The repetition of this error was facilitated by the world diffusion of Claude Bernard's work.

[Curare and Claude Bernard--how was his work introduced into Japanese scientific communities?].

"Curare and Claude BERNARD" is a well known set of physiology in several western scientific and medical communities. In using arrow poison curare as a tool of physiological anatomical approach, Bernard founded the experimental physiology of the nervous system. His famous experiments of using curare on frogs led to the observation of curare block in the myoneural junction of skeletal muscle. Bernard's achievements in curare research are recorded in full detail in his principal book of lectures, "Leçons sur les effets des substances toxiques et medicamenteuses (1857)". Nevertheless, Japanese physiological communities, attaching too much importance to German physiology between the end of the 19th century and the beginning of the 20th century, have mostly neglected the important work on curare done by Bernard, and the after-effect of this neglect is on-going in Japan. The aim of this article is to try to enlighten the communities with a small part of his lectures (i.e., arrow poison curare) described in "Leçons (1857)", which never reached us.

Curare: the South American arrow poison.

The history of curare is both curious and convoluted. A product of South American culture it emerged in the sixteenth century from the mists of antiquity at the same time as quinine, coca, and chocolate. Like quinine, at first came the extract but no plant, and later the plant but no chemical compound. It took more than 300 years and the efforts of many explorers and scientists to resolve the problem. These included Condamine, Humboldt, Brodie, Waterton, Bernard, Dale, Walker, and King. Finally, the pure compound d-tubocurarine was isolated from the liana Chondrodendron and synthesised. Its specific physiological action was blockade of the effect of acetylcholine at the neuro-muscular junction. Such a paralytic poison could be used to kill oneself or others. The bizarre plot to kill the Prime Minister, Lloyd George, during the First World War is described. Fortunately this nefarious plan was thwarted by the Secret Service!