Sodium Channels (I)

choi

Acquaint yourself with how modern medicine works, including drug development. My annotations use plain English, but I am unsure whether a person without knowledge in molecular biology -- not merely biology -- can comprehend them (annotations). The New Yorker article is easier to read, though (then again the writer, an MD, probably left the field after graduation, and definitely no MD, PhD.


Rivka Galchen, No-Pain Gains; The radical development of a new painkiller. New Yorker, June 2, 2025, at page 26.
https://www.newyorker.com/magazi ... rely-new-painkiller

Note: Rivka Galchen
https://en.wikipedia.org/wiki/Rivka_Galchen
("Galchen received her MD from Mount Sinai [1968- ; based in Manhattan (located in the interface between Harlem and Central Park); private; independent and not part of any university] in 2003. After medical school, she earned a MFA in 2006 from Columbia University") (citation omitted)
(a) "In the nineteenth century, pain and fever were treated with sodium salicylate, but the drug could cause nausea and a ringing in the ears, so a chemist for Friedrich Bayer & Co thought it would be worth trying variants on salicylic acid. He concocted the acetylsalicylic acid that we call aspirin. Other painkillers followed more zigzagging paths. In 1886, two German physicians decided to try naphthalene as a treatment for a patient with worms and a fever; the worms were unfazed, but the fever dropped. The physicians discovered that the pharmacist had accidentally given them the wrong substance, the later identification of which led to the development of acetaminophen, or Tylenol. The common epilepsy drug carbamazepine was developed to treat the shooting nerve pain of trigeminal neuralgia, which is described as feeling like a hatchet to the head and is often called the suicide pain."
(i) aspirin
(A) In salicylic acid, the stress is on the syllable "cy." The English word salicylic came from Latin noun feminine salix willow tree.
(B) salicylic acid
https://en.wikipedia.org/wiki/Salicylic_acid
(chemical structure at the top of page)
(C) In 1838, Italian chemist Raffaele Piriam, while working in Paris, isolated salicylic acid from salicin crystals (derived from extract of willow bark), but was unaware of its chemical structure.
(D) Spiraea
https://en.wikipedia.org/wiki/Spiraea
("commonly known as meadowsweets * * * Spiraea contain salicylates" but NOT acetylsalicylate)
(E) Manley J, A Look Back: the Wonder Drug. International Journal of Emergency Nursing, 26: 75 (2000)
https://www.intljourtranur.com/article/S0099-1767(00)70022-5/abstract
(abstract: " * * * In 1853, Charles Frederic Gerhardt, a French chemist, produced a new compound that was less irritating to the stomach by combining sodium salicylate * * * with acetyl chloride. Unfortunately, Gerhardt lost interest in his project and abandoned the research. Thirty years later, Felix Hoffmann, a German chemist with Friedrich Bayer & Co, began searching for a nonirritating pain reliever to ease his father's debilitating rheumatism. In 1897, he modified Gerhardt's structure and produced a pure and stable form of acetylsalicylic acid (ASA), more commonly known as aspirin (the name comes from 'a' for 'acetyl' and 'spir' for the spiraea plant) [because Hoffmann extracted salicylate from spiraea rather than willow] * * * ")
(F) "Bayer was founded as a dyestuffs factory in western Germany in 1863. It may seem counterintuitive, but many of today's pharmaceutical giants had their origins in dyes and fragrances, because they employed so many chemists." from the Web.
(ii) acetaminophen
(A) "in the 1880’s. German physicians Arnold Cahn and Paul Hepp were testing naphthalene as a treatment for [intestinal] worms. While the drug had no effect on the patient's worms, they noticed it did reduce fever. Upon further investigation they discovered that there had been a mistake. The naphthalene they thought they were administering was in fact acetanilide" (source: from the Web) which "is the N-acetylated derivative of aniline." In 1886 the two physicians marketed acetanilide despite the fact that the chemical is somewhat toxic to humans.
• paracetamol
https://en.wikipedia.org/wiki/Paracetamol
("In 1947, David Lester and Leon Greenberg found strong evidence that paracetamol was a major metabolite of acetanilide in human blood, and in a subsequent study they reported that large doses of paracetamol given to albino rats did not cause methemoglobinemia [the toxic side effect]. In 1948, Bernard Brodie, Julius Axelrod and Frederick Flinn confirmed that paracetamol was the major metabolite of acetanilide in humans, and established that it was just as efficacious an analgesic as its precursor. They also suggested that methemoglobinemia is produced in humans mainly by another metabolite, phenylhydroxylamine") (citations omitted)
• To reduce toxicity, a hydroxyl group was added at para position of acetanilide, resulting in acetaminophen (composed of acet- amino- and phenol).
• The acetaminophen is United States Adopted Name (USAN), see drug nomenclature
https://en.wikipedia.org/wiki/Drug_nomenclature
, whereas the name paracetamol is used in some other countries.
(B) pronunciation
• acetanilide
https://www.merriam-webster.com/dictionary/acetanilide
• aniline
https://www.merriam-webster.com/dictionary/aniline
acetaminophen
• The chemical aniline was "coined [in] 1841 by German chemist Carl Julius Fritzsche * * * from Portuguese [noun masculine] anil 'indigo shrub' * * * "  
https://www.etymonline.com/word/aniline
• aniline
https://en.wikipedia.org/wiki/Aniline
("Like most volatile amines, it has the odor of rotten fish. * * * It is toxic to humans. * * * while freshly purified aniline is an almost colorless oil, exposure to air results in gradual darkening to yellow or red, due to the formation of strongly colored, oxidized impurities. * * * Because an early source of the benzene from which they [aniline] are derived was coal tar, aniline dyes are also called coal tar dyes. * * * [section 5 History:] In 1840, Carl Julius Fritzsche (1808–1871) treated indigo with caustic potash and obtained an oil that he named aniline, after an indigo-yielding plant, anil (Indigofera suffruticosa).[29][30]")
(iii) carbamazepine
https://www.merriam-webster.com/dictionary/carbamazepine
(pronunciation)
also binds to voltage gated sodium channel, in the same mode of lidocaine 00 but is somewhat toxic (so its use in treatment is not in favor).

choi

From (b) onward, notations use a lot of italics, superscripts and subscripts. So I will use pdf attachment, serialized for several days.