ALKALOIDS.
The alkaloids extracted from vegetables are the ideal quintessences which the alchemical pharmacists of the sixteenth and seventeenth centuries sought so eagerly to obtain. Their characteristic property is that they are basic, that is, that definite salts can be formed from them by combination with acids. They all contain nitrogen, and have an alkaline reaction.
Of all the popular vegetable drugs opium was the one more than any other tortured to yield up its essence. The early laudanums and extracts of opium aimed at this result, and preparations, such as the Magisterium Opii of Ludovici of Weimar (born about 1625, and author of “Dissertations on Pharmacy”), were used in the belief that the quintessence had been in some degree secured. Robert Boyle experimented with opium with the object of extracting its essential principle. The process he adopted was first to treat the drug with calcined tartar (salt of tartar), and then extract with spirit of wine. By this means he obtained a solution which would be principally one of morphine.
In 1803 a French manufacturing chemist, working on an idea suggested by Vauquelin, produced a crystallisable salt which was at first supposed to be the active ingredient of opium. Experiments on animals seemed to confirm this opinion, and the salt of opium, or “sel narcotique de Derosne,” was believed to have solved the long-standing problem. The product was described in the “Annales de Chimie” of February, 1804. It was the substance now known as narcotine. Sertürner regarded it as meconate of morphium, a misapprehension which was corrected by Robiquet.
In December, 1804, Seguin, a chemist who had been a demonstrator under Fourcroy, and who subsequently got into trouble with Napoleon’s Government on charges of having enriched himself out of drug supplies to the Republican armies, read a paper to the Institute in which he described a process which would yield morphine. For some unexplained reason that paper was not published until 1814. Meanwhile Friedrich Wilhelm Adam Sertürner, a pharmacist of Eimbeck, in Hanover, had been working on Derosne’s salt, and had investigated more accurately than anyone before him the composition of opium. His first report was published in 1806, and in that he announced the discovery of “opium-säure” (opium acid), but in 1816 he named this product “meconic acid,” and explained how it was combined with an alkaline base which he called “Morphium.” He described this as analogous to ammonia, and prepared several salts from it. He came near to losing his life in the course of his experiments as, misled by the comparative harmlessness of Derosne’s salt, he had ventured on dangerous doses of his own product. Consequently he was able to determine very accurately the therapeutics of morphine at the same time that he announced its discovery.
“I flatter myself,” wrote Sertürner in 1816, “that chemists and physicians will find that my observations have explained to a considerable extent the constitution of opium, and that I have enriched chemistry with a new acid (meconic) and with a new alkaline base (morphium), a remarkable substance which shows much analogy with ammonia.”
Sertürner’s discovery excited much interest and emulation, and its importance was fully endorsed when, in 1831, the French Institute awarded to him a prize of 2,000 francs “for having opened the way to important medical discoveries by his isolation of morphine and his exposition of its character.”
Before Sertürner had definitely established the nature of alkaloids, Vauquelin had separated from tobacco a substance which he regarded as its active principle, and which was undoubtedly an impure nicotine. This was in 1809. The alkaloidal character of this extract was not, however, recognised until 1828, when Posselt and Reimann produced it in a pure form.
Vauquelin had in 1812 extracted daphnine from mezereon root, and in describing his experiments had alluded to its alkaline character. For this reason the credit of having been the first to have discovered an organic alkali has been attributed to him; and when in 1818 Pelletier and Caventou discovered an alkaloid in St. Ignatius’s beans, to which they gave the name of strychnine, they stated that it had been their original intention to designate the substance Vauqueline in honour of the celebrated chemist who had first established the existence of an organic alkali. It had, however, been pointed out to them by distinguished members of the Academy that it would have been a doubtful compliment to associate such an honoured name as that of Vauquelin with such an evil (malfaisant) substance as this new product.
A number of chemists narrowly missed the discovery of quinine. As early as 1746 Count Claude de la Garaye obtained from cinchona bark a crystalline salt which he termed sel essentiel de quinquina. Two other French chemists, Buquet and Cornette, subsequently introduced another sel essentiel de quinquina. Both these products were simply kinate of lime. A Swedish physician named Westerling announced in 1782 that he had discovered the active principle of cinchona, and he gave it the designation of vis coriaria. His product was in fact cinchotannic acid. Seguin perhaps made the worst mistake of all the investigators in coming to the conclusion that what was precipitated by tannin was the essence of cinchona from a medicinal point of view, and he actually recommended that gelatin should be substituted for cinchona in cases when price was an object. Fourcroy made several attempts to ascertain the true chemical constitution of the bark. In 1790 he separated a resinous principle, mixed with some colouring matter, since called cinchonic red. This he at first supposed was the essential medical constituent of the bark. Vauquelin later adopted this erroneous theory, and so missed his way. In 1792 Fourcroy got nearer to the truth when he observed incidentally that the water in which the bark had been macerated turned litmus paper green; and he also remarked that lime water caused a greenish precipitate in the infusion. He did not pursue the investigation, but his comment on what he had stated is noteworthy. “These researches,” he said, “will no doubt lead to the discovery one day of an anti-periodic febrifuge, which once known may be extracted from various vegetables.” Berthollet followed on Fourcroy’s lines, but came to the conclusion that the precipitate which lime water gave with decoctions of cinchona was magnesia, which he believed was a constituent of the bark in combination with hydrochloric acid.
In 1811 Gomez, of Lisbon, described a crystalline substance which Dr. Duncan, of Edinburgh, had obtained from certain species of cinchona, and gave to this product the name of cinchonine. Lambert later prepared it in a state of considerable purity. But neither of these chemists suspected its alkaline nature. In 1820 Pelletier and Caventou studied the whole chemistry of cinchona and succeeded in showing that the cinchonine of Gomez was a mixture of two alkaloids, to the second of which they gave the name of quinine. Quinidine was isolated by Henry and Delondre in 1833, and cinchonidine by Winckler in 1844, but the name of the latter was given by Pasteur in 1853. Pasteur also produced the alkaloidal derivatives cinchonicine and quinicine.
Robiquet had the idea that as the coffee plant belongs to the same family of plants as the cinchonas it might be possible to find quinine in coffee. In searching for it he isolated caffeine. This was in 1821. In 1827 Oudry found an alkaloid in tea and called it theine. Jobst and Mulder in 1838 proved that these alkaloids are identical. It is now recognised that the alkaloids of cocoa, of guarana, and of Paraguay tea are all the same substance, or closely related.
Pelletier and Caventou isolated strychnine from the St. Ignatius beans in 1818, and brucine from false angostura bark (Brucæa anti-dysenterica) in 1819; in the same years they obtained veratrine from cevadilla seeds and white hellebore root; but it would appear that in their investigation of cevadilla seeds, which was the first to yield the alkaloid, they were preceded by a very short time by Meissner. Pelletier and Magendie produced emetine from ipecacuanha in 1817, and Pelletier alone is credited with narceine in 1832. Codeine was discovered by Robiquet in 1821 when he was examining a new process for obtaining morphine which had been suggested by Dr. William Gregory, of Edinburgh. Belladonna had been studied by Vauquelin and many chemists after him, but it was not until 1833 that atropine in a state of purity was isolated from it. This was accomplished simultaneously by Geiger and Hess, two German chemists, and by Mein, a German pharmacist.