Not even biologists are aware about how benzodiazepine was discovered..
Obituary: Leo Sternbach, inventor of Valium, died on September 28th, aged 97. Economist, Oct 13, 2005.
www.economist.com/node/5017018
Note:
(a) "The ancient Greeks * * * knew the calming oblivion of eating the lotus or sipping nepenthe."
(i)
(A) lotus-eaters
en.wikipedia.org/wiki/Lotus-eaters
(fruits and flowers were narcotic, causing the people to sleep in peaceful apathy; Because the Greek word lôtos can refer to several different plants, there is some ambiguity as to which "lotus" appears in the Odyssey)
(B) Lotus-Eater. Encyclopaedia Britannica, undated.
www.britannica.com/EBchecked/topic/348576/Lotus-Eater
(ii)
(A) nepenthe
en.wikipedia.org/wiki/Nepenthe
(B) nepenthe (n; Latin nepenthes, from Greek nēpenthes, neuter of nēpenthēs banishing pain and sorrow, from nē- not + penthos grief, sorrow)
www.merriam-webster.com/dictionary/nepenthe
(b) "The industrial and French revolutions * * * saw De Quincey on opium, Coleridge on laudanum and Davy, in his chemical laboratory, giggling and whooping helplessly as he sniffed nitrous oxide gas."
(i) Thomas De Quincey
en.wikipedia.org/wiki/Thomas_De_Quincey
(1785 –1859; best known for his Confessions of an English Opium-Eater (1821)
(ii)
(A) Samuel Taylor Coleridge
en.wikipedia.org/wiki/Samuel_Taylor_Coleridge
(1772 – 1834; English)
(B) laudanum (n)
www.etymonline.com/index.php?term=laudanum
* tincture (n; Middle English, from Latin tinctura act of dyeing, fromtinctus, past participle of tingere to tinge):
"a solution of a medicinal substance in an alcoholic solvent"
www.merriam-webster.com/dictionary/tincture
(iii) Humphry Davy
en.wikipedia.org/wiki/Humphry_Davy
(1778-1829; Cornish; “Davy would become addicted to [nitrous oxide (laughing gas)]. The gas was first synthesized by the English natural philosopher and chemist Joseph Priestley in 1772”)
(c) "for the problem with all tranquillisers up till then [before Valium], from henbane and absinthe to barbiturates, was that they gave unpleasant side effects at moderate doses and, at larger ones, killed you.
(i) For henbane, see Hyoscyamus niger
en.wikipedia.org/wiki/Hyoscyamus_niger
(commonly known as henbane; originated in Eurasia; "The name henbane dates at least to AD 1265. The origins of the word are unclear, but 'hen' probably originally meant death rather than referring to chickens"/ "Common effects of henbane ingestion in humans include hallucinations, dilated pupils, restlessness, and flushed skin")
(A) bane (n)
www.merriam-webster.com/dictionary/bane
(B) The active ingredients of Hyoscyamus niger are tropane (specifically, atropine and scopolamine)
atropine
en.wikipedia.org/wiki/Atropine
(extracted from Atropa belladonna; atropine counters acetylcholine, “the main neurotransmitter used by the parasympathetic nervous system”/ section 1 Name)
(ii) Regarding absinthe.
(A) absinthe
en.wikipedia.org/wiki/Absinthe
(includes flowers and leaves of Artemisia absinthium; originated in Switzerland in the late 18th century; The chemical compound thujone, although present in the spirit in only trace amounts, was blamed for its alleged psychoactive effects)
thujone
en.wikipedia.org/wiki/Thujone
(found in Artemisia absinthium, among other plants; “Thujone is a GABAA receptor antagonist. By inhibiting GABA receptor activation, neurons may fire more easily”)
“Thujone is a GABAA receptor antagonist.” This means thujone (an antagonist) and GABA (protagonist) compete with each other--due to similarity in 3D chemical structures--to bind the GABA receptor.
(B) Höld KM et al, Detoxification of alpha- and beta-Thujones (the active ingredients of absinthe): site specificity and species differences in cytochrome P450 oxidation in vitro and in vivo.
www.ncbi.nlm.nih.gov/pubmed/?term=absinthe+active+ingredients
(“Alpha- and beta-Thujones are active ingredients in the liqueur absinthe and in herbal medicines and seasonings for food and drinks. Our earlier study established that they are convulsants and have insecticidal activity, acting as noncompetitive blockers of the gamma-aminobutyric acid (GABA)-gated chloride channel”)
(d) "His employer, Hoffman-La Roche, was in a race with Wallace Pharmaceuticals. Wallace had already brought out a pill, Miltown"
(i) Hoffman-La Roche
en.wikipedia.org/wiki/Hoffman-La_Roche
(Founded in 1896 by Fritz Hoffmann-La Roche; Headquarters Basel (where the Swiss, French and German borders meet), Switzerland)
(A) German English dictionary
hof (noun masculine): “court, farm, house”
(B) French English dictionary
roche
(noun feminine; from from Medieval Latin rocca, of uncertain origin): "rock"
en.wiktionary.org/wiki/roche
(ii) About Us. Wallace Pharmaceuticals, undated
www.wallacepharmaceuticals.com/aboutus.html
("In 1880, Carter Medicine Company was born [formed by Dr John Samuel Carter]. * * * In 1935, the innovative contributions from a research chemist in Princeton, NJ, John H Wallace, helped the company top the $1 million mark for the first time in history * * * Following introduction [of Miltown, a tranquilizer that was the first of its kind] in 1955, Miltown's sales doubled and tripled each of the subsequent five months")
is located at Somerset, New Jersey.
(e) “In his wilful way (“I always did just what I wanted to do,” he said later), he turned to research he had started as a student, at Krakow University, into a class of compounds called benzodiapenes. At the time, he had thought he might make synthetic dyes with them.”
For Krakow University, see Jagiellonian University
en.wikipedia.org/wiki/Jagiellonian_University
(location Kraków, Poland; founded in 1364 by Casimir III the Great, one of the oldest universities in the world; the university was renamed as Jagiellonian University to commemorate Poland's Jagiellonian dynasty [1386-1572])
(f) “Over two years, he tested 40 [benzodiapene/ ~pine] compounds. They turned out to be pharmacologically inert. * * * In 1956 Mr Sternbach, fiddling with yet another benzodiazepine, treated it with methylamine, made a white crystalline powder, labelled it Ro 5-0690 and put it away on a shelf. He was ordered to stop messing about, and to develop antibiotics instead. He was well aware, however, that he had made something interesting. When he tested the powder on mice they no longer ran up a steep incline to get a reward, nor tumbled down it in a stupor, but ran around, happy and alert, at the bottom, as if the rat-race did not exist. Under pretence of finding it accidentally, and being about to throw it away, Mr Sternbach took his powder to the head of pharmacology for testing. He, too, was excited to see the way the mice behaved. Cats relaxed when dosed, and nervous old folk became tranquil, with no side effects. The new drug, named Librium, was approved for use in 1960. Three years later a simpler version, several times stronger, was developed by Mr Sternbach and called Valium. This became astonishingly popular. Between 1969 and 1982, it [valium, a little yellow pill (by Hoffmann-La Roche)] was the most prescribed drug in America”
chlordiazepoxide
en.wikipedia.org/wiki/Chlordiazepoxide
(was discovered by accident when in 1957 tests revealed that the compound had hypnotic, anxiolytic and muscle relaxant effects; in 1959 marketed under the brand name Librium; Following chlordiazepoxide, in 1963 diazepam hit the market under the brand name Valium)
(g) “Stars competed to admit their dependence. Elizabeth Taylor said she swallowed hers with Jack Daniels”--the whiskey.
(h) “He [Sternbach] claimed 241 patents, including Mogadon, a sleeping pill, and Klonopin, for epilepsy. * * * Mr Sternbach himself got a dollar for each discovery (paid for resigning the patent rights)”
(i) Mogadon was the brand name of nitrazepam and Klonopin, the brand name of Clonazepam (both by Hoffmann-La Roche and both chemically benzodiazepine).
(ii) The resign” in the clause “resign the patent rights” is a verb meaning “sign again.”
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发表于 6-17-2014 17:25:57
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