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~ I~m~III~111 200608197 CSIRO PUBLISHING www.publish.csiro.au/joumals/hras His/orical Records oJAus/ralian Science, 2006, 17, 31-69 Duboisia myoporoides: The Medical Career of a Native Australian Plant Paul Foley Prince ofWales Medical Research Institute, Barker Street, Randwick, NSW 2031, Australia. Email: [email protected] Alkaloids derived from solanaceous plants were the subject ofintense investigations by European chemists, pharmacologi~ts and clinicians in the second half ofthe nineteenth century. Some surprise was expressed when it was discovered in the 1870s that an Australian bush, Duboisia myoporoides, contained an atropine like alkaloid" 'duboisine'. A complicated and colourful history followed. Duboisine was adopted in Australia, Europe and the United States as an alternative to atropine as an ophthalmologic agent; shortly afterwards, it was also estecmed as a potent sedative in the management ofpsychiatric patients, and as an alternative to other solanaceous alkaloids in the treatment ofparkinsonism. The Second World War led to renewed interest in Duboisia species as sources of scopolamine, required for surgical anaesthesia and to manage sea-sickness, a major problem in the naval part ofthe war. As a consequence ofthe efforts of the CSIR and of Wilfrid Russell Grimwade (1879-1955), this led to the establishment of plantations in Queensland that today still supply the bulk of the world's raw scopolamine. Following the War, however, government support for commercial alkaloid extraction waned, and it was the interest ofthe German firm Boehringer Ingelheim and its investment in the industry that rescued the Duboisia industry in the mid I950s, and that continues to maintain it at a relatively low but stable level today. 'It is to be regretted that scientific men in this colony have paid so little attention to the subject of Medicinal Botany. Surrounded, as we are, by shrubs and plants possessing medicinal properties, there is a wide field for investigation; and, no doubt, it will be found in time to come, that we have been sending to distant countries for expensive medicines, whilst remedies equally efficacious might be provided close at hand in all their native freshness.' William Woolls, ACon/ribu/ion /0 the Flora oJAustralia (1867), p. 94. Introduction: Solanaceous Plants achieved particular prominence and The Solanaceae family includes a fascinat remained in standard pharmacopoeias until the mid-twentieth century: deadly ing variety of plants. Some members nightshade (Atropa belladonna), henbane including the mandrake (Atropa mand-, (Hyoscyamus niger) and the thorn-apple ragora), Russian henbane (Hyoscyamus (Datura stramonium). The isolation of the albus) and scopola (Scopolia carniolica) active components ofthese plants attracted - have been employed for centuries to a great deal of attention at the end of the induce hallucinations and in 'witches' eighteenth century, but it was only in the salves', in religious contexts and as instru-, middle of the nineteenth that what might ments of crime, while others - including be termed the first golden age of alkaloid the tomato (Lycopersicum esculentum), isolation unfolded.' Within a short time, a potato (Solanum tuberosum) and capsicum range of alkaloids had been isolated from (Capsicum frutescens) - have found various Solanaceae, each named for the favour in the kitchen. plant from which it was derived: 'solanine' A number of s'oIanaceous (solamen = from Solanum nigrum was the first in 'comfort-giving') plants have also long ]820, followed by 'atropine' from Atropa played significant roles in European medi belladonna in ]83], 'hyoscyamine' from cine, both in folk traditions and in so Hyoscyamus niger, and so on.2 Analytical called 'school medicine'. Certain of these techniques available at this time did not © Australian Academy of Science 2006 10.1071/HR06001 0727-3061/06/010031 Copyright of Full Text rests with the original copyright owner and, except as permitted under the Copyright Act 1968, copying this copyright material is prohibited without the permission of the owner 32 Historical Records ofAustralian Science, Volume 17 Number I permit determination oftheir structures, so nized that many of the solanaceous alka that these alkaloids were defined accord loids were, in fact, identical with one or ing to estimated absolute chemical compo other of the two major tropane alkaloids, sition and the physical characteristics of atropine (= racemic hyoscyamine) and their salts. By the close of the nineteenth scopolamine (= hyoscine; Fig. l). These century, however, it was generally recog- alkaloids were widely employed in the 38 tropine, A =H 3b acetyllroplne, A = COCH3 3c butroplne, A =COCH(CH3)2 3d valtropine, A = 18 (-)-scopolamlne (hyoscine) 28 (-)-hyoscyamine COCH(CH 3)CH2CH 3 lb atroscine ((±) -hyoscine)· 2b atropine ((±)-hyoscyamlne) 3e tropine nonanoate, A = CO(CH 2hCH3 6a poroidine, A =COCH~H(CH3)2 4 norscopolamlne (norhyoscine) 5 noralropine 6b Isoporoldine, A = COCH(CH3)CH 2CH3 r"' . "'''n- r"' nYD ro ":~~ 7 aposcopolamine 8 apoalropine 9 valeroidine (apohyoscine) 10 6~-hydroxyhyoscyamine 11 7~-hydroxyhyoscyamlne 12 liltorine 13 ligloidlne 14 ligloyltrop(e)lne Figure 1. Tropane alkaloids identified in Duboisia myoporoides. *Included for completeness, but not identified in D. myoporoides. Duboisia myoporoides and Medicine 33 second half of the nineteenth century as tunate Burke and Wills expedition to Aus- . sedatives and hypnotics (especially in psy tralia's interior,lo who supplied material chiatric patients), for which reason they to W. Johnston in Tasmania and a pow were also used as antiparkinsonian agents, dered sample to the Rostock-born bota and atropine was also utilized in ophthal nist Ferdinand Mueller (1825-1896) in mology for its mydriatic (pupil-dilating) Melbourne. 11 Bancroft independently properties.3 obtained material from the vicinity of Alkaloid nomenclature was often the Cooper's Creek (north-eastern South Aus subject of heated and confusing debate, tralia), and reported his preliminary and a particular instance is relevant to the investigation of its physiological proper present discussion. 'Hyoscine' - first pre ties to the Queensland Philosophical paredby Albert Ladenburg in 18804- and Society in 1872.12 A few years later, 'scopolamine' - first isolated by Ernst Bancroft serendipitously obtained Schmidt from Scopola species in 18885 samples of the source plant, which and subsequently also from Duboisia Mueller identified a short time later as the myoporoides leaf procured in the eastern Central Desert tree Duboisia hopwoodii, German city of Gorlitz6 - are synonyms, recently (re)named by Mueller himself. 13 but a colourful controversy regarding their An alkaloid isolated from D. hopwoodii, identity raged, especially in Germany, 'piturine', was initially identified by the from their discovery until the early twenti French chemist A[rthur-Leon?] Petit with eth century. Both names continued to be nicotine,14 but D. hopwoodii was later used for many decades, the choice often found also to contain the more potent seemingly dependent on the nationality of d-nornicotine. 15 More recently it has been the writer,7 and by the mid-1920s, the recognized that 'pituri' in most parts of name 'hyoscine' had largely been aban Australia is not, in fact, derived from doned except in England and associated D. hopwoodii, but rather from local Nico countries.8 For the sake of clarity, I shall tiana species (also members of the generally employ 'scopolamine' in this Solanaceae family).16 paper, except where 'hyoscine' appears-in In a letter to Bancroft read to the a directly cited text. Queensland Philosophical Society in 1877, Mueller commented: Duboisia Now an interes1ing field opens to Late additions to the Solanaceae family Dr. Bancroft for further research. Let the were identified in the mid-nineteenth Doctor try the foliage of Duboisia myopo century in a corner of the world then roides, as he could easily, for a little pay regarded as both exotic and remote: Aus ment, get a blackfellow to administer small doses of that plant to. There could be no tralia. Joseph Bancroft (1836-1894), danger in the experiment if the quantity is medical practitioner and the first of a given cautiously. I fancy that the properties family line of medical naturalists,9 had ofthe Duboisias will prove similar to those 17 become intrigued by the properties of ofstrarnonium. pituri, or 'native tobacco', a drug tradi The recommended species, D. myopo tionally employed by Aborigines as a roides (Figs 2,3), had been first described in chewed intoxicant allowing long periods 1810 by the distinguished Scottish naturalist of work without food or rest, similar to Robert Brown (1773-1858) in his report on the chewing of coca in central America. the botany of New Holland (1802-1805), Pituri was first placed at the disposal of conducted in conjunction with Flinders' European investigators by John King circumnavigation of the continent. Brown (1841-1872), sole survivor of the unfor- had collected his sample in the Sydney- 34 Historical Records ofAustralian Science, Volume 17 Number 1 Hunter region; the species designation South Wales botanist Joseph Maiden,19 but myoporoides derived from its resemblance it could also refer to Charles Du Bois to an unrelated east coast plant, Myoporum (1656-1740), treasurer of the East India acuminatulIl, but Brown did not explain his Company (1702-1737), who had a botani christening the genus Duboisia. ls It may cal garden at

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