John Chassar Moir (1900-1977) and the discovery of ergometrine

Dunn, P M

doi:10.1136/fn.87.2.f152

Cited by 8 publications

(3 citation statements)

References 3 publications

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“…Browne arranged for his assistant Dr John Chassar Moir to carry out tests. 42,43 In accepting the task, Chassar Moir asserted that a clinical trial comparing ergotoxine with ergotamine would be impossible because in the puerperium, for example, the rate of involution varies in accordance with so many conditions, e.g. anaemia, state of health of the patient, history, degree of post partum haemorrhage, presence and degree of sepsis and so on, that it would be impossible, I think, to say to what extent any drug influences it.…”

Section: Part 2: Methodological Aspects Of the Work Of The Mrc Therapmentioning

confidence: 99%

Why the MRC therapeutic trials committee did not introduce controlled clinical trials

Toth¹

2015

J R Soc Med

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Section: Part 2: Methodological Aspects Of the Work Of The Mrc Therapmentioning

confidence: 99%

Why the MRC therapeutic trials committee did not introduce controlled clinical trials

Toth¹

2015

J R Soc Med

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“…On stealing a glance into the patient's room, he found her unperturbed by the experiment, quietly eating lunch. 18 The experiments were repeated a number of times and the liquid extract's potency was maintained. There was, in particular, no weakening of the response with repetitive dosing.…”

Section: Ergometrinementioning

confidence: 99%

The history of ergot of rye (Claviceps purpurea) II: 1900–1940

2009

JRCPE

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Ergot, in 1900, was a 'chemical mess'. Henry Wellcome, the pharmaceutical manufacturer, invited Henry Hallett Dale, a physiologist, to join his research department and solve this problem. Dale, in turn, recruited an outstanding group of scientists, including George Barger, Arthur Ewins and Harold Dudley, who would make distinguished contributions not only to the chemistry of ergot but also to the identification of acetylcholine, histamine and tyramine and to studies on their physiological effects. Initially Barger and Dale isolated the compound ergotoxine, but this proved to be a false lead; it was later shown to be a mixture of three different ergot alkaloids. The major success of the Wellcome group was the discovery and isolation of ergometrine, which would prove to be life-saving in postpartum haemorrhage. In 1917 Arthur Stoll and his colleagues started work on ergot at Sandoz Pharmaceuticals in Basel. A series of important results emerged over the next 30 years, including the isolation of ergotamine in 1918, an effective treatment for migraine with aura.

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“…The long history of ergot as a cereal and grass parasite, adversely affecting humans and agricultural ruminants, gradually evolved to include beneficial pharmaceuticals for which specific cultivation on rye on an industrial scale in Central Europe (e.g., in Germany, Czechoslovakia, and Switzerland) was supplemented also by sclerotia salvaged via cereal seed cleaning. In England, in the context of the developments of ergometrine in obstetrics [1], Burroughs, Wellcome & Co processed raw ergot for pharmaceuticals during the first half of the last century and explored agricultural cultivation of Claviceps purpurea (Fr.) Tul.…”

Section: Introductionmentioning

confidence: 99%

Comparative Ergot Alkaloid Elaboration by Selected Plectenchymatic Mycelia of Claviceps purpurea through Sequential Cycles of Axenic Culture and Plant Parasitism

Mantle

2020

Biology

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Ergot alkaloids have an established place in plant pathology and toxicology. As pharmaceuticals, their sourcing is via natural or managed agricultural occurrence of sclerotia of Claviceps purpurea (Fr.) Tul. or through industrial fermentation processes with other Claviceps. The key factor for biosynthesis is differentiation of a particular mycelial anatomy. Previous study of these fungi from two disparate English grass genera, Spartina and Phragmites, has shown that only mycelia expressing a plectenchymatic sclerotium-like anatomy in specific axenic culture conditions elaborated ergot alkaloids, and then only as far as lysergic acid. The present report describes sequential cycles of axenic and parasitic cultivation for wild isolates from Dactylis and Alopecurus with intervention of a single ascospore step. This confirms the homozygous character of C. purpurea and defines several potential experimental axenic and parasitic conditions within the species for comparing genomic aspects of partial or full biosynthesis of cyclic tri-peptide alkaloids. Whereas Alopecurus ergot isolates readily parasitized rye, use of Dactylis isolates as inoculum for rye ovaries failed to cause the usual sphacelial fructification but supported growth of exceptionally thin sclerotia, sometimes two in a floret, with low alkaloid content attributed to reduced medullary component. However, after two cycles of axenic and rye-parasitic cultivation, and consistent re-selection of the plectenchymatic character in axenic mycelia, typical growth of ergot sclerotia occurred on rye. Caution thus seems necessary in tests for putative host specificity in any taxonomic realignments within the classical concept of C. purpurea. A Dactylis ergot isolate was also uniquely shown to parasitise the plumule of germinating rye seeds confirming the susceptibility of apical tissues. A key biosynthetic feature of a mycelial glyceride oil, rich in ricinoleic acid, as a prelude to axenic and parasitic formation of ergot alkaloids by C. purpurea is emphasised.

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John Chassar Moir (1900-1977) and the discovery of ergometrine

Cited by 8 publications

References 3 publications

Why the MRC therapeutic trials committee did not introduce controlled clinical trials

Why the MRC therapeutic trials committee did not introduce controlled clinical trials

The history of ergot of rye (Claviceps purpurea) II: 1900–1940

Comparative Ergot Alkaloid Elaboration by Selected Plectenchymatic Mycelia of Claviceps purpurea through Sequential Cycles of Axenic Culture and Plant Parasitism

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