The leaves of Duboisia myoporoides, Robert Brown.
COMMON NAMES: Corkwood elm, Orungurabie, Ngmoo (native names).
Botanical Source.—This is a large shrub found in Australia and New Caledonia. It has alternate, smooth, entire leaves, narrowed into a short leaf-stalk, which is articulated to the branches. The flowers are small, white, and disposed in large terminal panicles. The calyx and corolla are 5-parted, with obtuse lobes. The stamens are didynamous, with the rudiment of a fifth, and bear 1-celled anthers. The fruit is a small, black, 2-celled berry, which contains a few reniform, rough seeds. The genus Duboisia is intermediate between the natural orders Solanaceae and Scrophulariaceae, and was referred to the former by the older authors; Bentham, in the Flora of Australia, classes it with the latter, but more recent developments regarding a natural constituent (duboisine), seem to indicate that its true place is among the Solanaceae.
History.—The honor of introducing this drug to the profession belongs to Dr. J. Bancroft, of Brisbane, Australia, who presented the plant to Baron von Mueller for botanical identification, and who, at his suggestion, experimented with it as a therapeutical agent, and presented the first paper on the subject to the Queensland Philosophical Society of Australia, in October, 1877. Shortly afterward, he (Bancroft) sent specimens of the plant to the Museum of the British Pharmaceutical Society. In March, 1878, Mr. E. M. Holmes read a paper before the society on Duboisia myoporoides, its botanical history, etc., and nearly at the same time, a communication appeared in the London Lancet from Drs. Ringer and Tweedy, detailing a line of experiments upon its therapeutical action, in which the previous report of Dr. Bancroft was corroborated in every particular. Shortly afterward, Gerrard, of England, and Petit, of France (see Pharm. Jour. Trans., , Vol. VII, p. 787), almost simultaneously announced the discovery of an alkaloid called duboisine or duboisina. F. von Mueller and L. Rummell also announced their discovery of duboisine from D. myoporoides (Jour. Chem. Soc., January, 1879, p. 32), but as their alkaloid is an oily, volatile base, its identity with duboisine is questionable.
Chemical Composition.—The chief constituent of this leaf, called duboisine by its discoverers, was found by Prof. A. Ladenburg to be identical with hyoscyamine (C17H23NO3) (Ber. d. Deutsch. Chem. Ges., 1880, p. 1257). The properties of duboisine are therefore described under hyoscyamine (see Hyoscyamus). Another isomeric alkaloid was obtained by Merck, called pseudo-hyoscyamine, forming yellowish needles of an acrid, bitter taste, soluble in alcohol and chloroform, slightly soluble in ether. Its melting point is 133° to 134° C. (271.4° to 273.2° F.), while hyoscyamine (duboisine), melts at 106° to 108° C. (222.8° to 226.4° F.) (Merck's Index, 1896).
Action, Medical Uses, and Dosage.—The action of duboisia upon man and animals is very similar to that of belladonna, hyoscyamus, etc. Dogs and cats to which it has been administered, almost immediately commence walking with difficulty, stumbling over the least obstacle as though they were blind, and falling asleep as soon as they are left at rest, having the pupils largely dilated; these results also followed its introduction into the system by hypodermatic injection. Large doses internally, or by subcutaneous injection, occasion large pupillary dilatation, dryness of the mouth and throat, increase the number of pulsations, and give rise to general debility, vertigo, and cephalalgia; the results are the same with man as with animals. The alkaloid, duboisine, produces similar effects. The sulphate of this alkaloid, subcutaneously injected in large doses, occasions a sort of intoxication, mental derangement, pupillary dilatation, incoordination of muscular motion, relaxation of the vesical and anal sphincters, and an increased temperature at first, succeeded by a very marked diminution.
As an internal remedy, neither the shrub nor its alkaloid (except as hyoscyamine) have come into general use. Used in this manner, duboisia will be found to possess properties similar to those of belladonna and its congeners. Duboisine, and its sulphate, are more commonly employed in this country, principally in ocular therapeutics; it has been found by Drs. Wecker and Galezowski, of Paris, to be a prompt and unirritating mydriatic, the mydriasis being accompanied with paralysis of the ciliary muscle, and consequently an absolute loss of accommodation. The mydriasis produced does not appear to annoy the patient, nor to last as long as when occasioned by atropine; nor does the employment of the agent give rise to the intense conjunctival irritations (follicular conjunctivitis and eczema of the lids) so often following the application of atropine. It may be employed in all maladies of the eyes in which atropine is indicated, being contraindicated in glaucomatous conditions, and in diseased conditions of the fundus. From 2 to 4 grains of the sulphate of duboisine are dissolved in 1 fluid ounce of water, and of this solution from 2 to 5 drops may be instilled into one or both eyes as required; the mydriatic effect commences in a few minutes. The solution of the sulphate of duboisine has likewise been successfully employed, by hypodermatic injection, for checking the pathological sweatings common to phthisis, etc., and also as an antidote to poisoning by mushrooms, antagonizing the paralyzing effect of muscarine on the heart. It is reputed palliative in exophthalmic goitre. The dose to be used will differ with various individuals, from the 1/80 or 1/30 to 1/20 grain. The beginning dose should rarely exceed 1/70 grain. For ophthalmic use 1 to 4 grains to 1 ounce of distilled water. Care should be bad in its use, as occasionally untoward symptoms have been produced by reduced applications (see also Atropinae Sulphas, Belladonna, and Hyoscyamus).
Specific Indications and Uses.—A substitute for atropine as a mydriatic, and to check colliquative sweating; antagonizes muscarine; mushroom poisoning.
Related Species.—Duboisia Hopwoodii, F. von Mueller. This is the Australian Pitury, also known as piturie, pedgery, pitchiri, pitchery, and bedgery. It has long been known that the natives of Central Australia use the leaf of some shrub in order to invigorate themselves, after long marches, or when they are desirous of undergoing great fatigue, as during a battle. This leaf is used as a masticatory by the Australians in a manner similar to that of the coca leaves by the South Americans. It is asserted that when the natives chew pitury "in company," the quid is passed from one to another until all are satisfied, when one of the number preserves it by sticking it behind his ear (Maiden, Australian Useful Plants). Dr. Bancroft, of Brisbane, in 1872, made some physiological experiments with authentic specimens of pituri; yet the source of the drug was unknown until 1877, when Baron von Mueller identified it from a specimen of the leaves of the plant submitted to him by Mr. W. O. Hodgkinson; accordingly, the pitury is Duboisia Hopwoodii, F. Mueller, a shrub found sparingly "from the Darling River and Barcooto to West Australia." But little is known of this shrub, as it grows in a country difficult of access. Staiger is probably the first who isolated from Duboisia Hopwoodii piturine, an alkaloid with which the "duboisine" of F. von Mueller and F. Rummel (see above), is most probably identical. A. W. Gerrard, in 1880, independently discovered the alkaloid piturine in this plant (Pharm. Jour. Trans., 1880). When fresh it smells like nicotine, but when older has a smell of pyridine. Its vapors affect the mucous membranes and cause violent headache. Some authorities (e. g., Petit, Jour. Pharm. Chim., 1879, p. 338), consider piturine identical with nicotine. Prof. Liversidge, however, points out some differences in their reactions, but otherwise they are quite similar (Amer. Jour. Pharm., 1881, p. 357). Piturine (C12H16N2), was obtained by him in the amount of 1.0 and 2.4 per cent. It is a colorless alkaloid, volatile at ordinary temperatures, changing to yellow and brown rapidly when exposed to air and sunlight. It is soluble in water, alcohol, and ether, is slightly heavier than water, and forms salts with acids, which, with oxalic acid, are capable of crystallizing. Its salts gradually lose the alkaloid by evaporation. Piturine is reported to antagonize the action of muscarine on the heart, but not so promptly as atropine. Dr. Bancroft states that this drug arrests the respiration of animals, and thus causes their death. The action of pitury is essentially different from that of duboisia. Applied to the eye, it first contracts, and then widely dilates the pupils; internally, small doses contract the pupils, while large doses produce a wide dilatation. Faintness, giddiness, trembling, pallor, quickened and shallow breathing, increased heart action, and sweating, are induced by it, and if the dose be large, drowsiness, ptyalism, spasmodic muscular twitching, and spasmodic rigidity of the limbs are among its effects.