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Hopeine: Hazy Hallucinations and Foolish Impudence
Eh, it's just going to get worse.
Springmuhl's Concentrated Produce Company reported the discovery of a new narcotic, hopein or hopeine, derived from wild American hops. This discovery was the result of attempts to produce condensed beer. Independent analysts determined that samples of hopeine consisted of morphine or a mixture of morphine and cocaine. B. H. Paul of the Pharmaceutical Journal wrote: "It is intelligible that a new narcotic preparation of that kind might be introduced under a fancy name and at a high price; but the attempt to introduce upon a pseudo-scientific basis an article that is only a mixture of two well-known substances is, I may say, a piece of foolish impudence that almost passes belief."
The London Medical Record, August 15, 1885, Page 341
Hopein, the Narcotic Principle of Hops.—-An article on this subject appears in Der Fortschritt, June 20, 1885 [page 252]. It has long been supposed that hops contain a narcotic principle, the isolation of which however failed, until W. Williamson and Springmuehl first succeeded in obtaining from American hops a new alkaloid, hopein, of eminently narcotic properties, barely inferior in power to morphia, without, however, the objectionable subsequent effects of the latter. The experiments connected with concentration in vacuum of strongly hopped English beer and the brewing of condensed beer, lead to the conviction that certain qualities of hops contain small quantities of a narcotic alkaloid, in its properties closely related to morphia. Just as only certain kinds of poppies grown in particular climates yield a satisfactory quantity of morphia, so also the larger or lesser proportion of the narcotic principle of the hops vary according to the place and 'he manner of cultivation of this plant; whereas German hops possess only traces of hopein, the richness in this alkaloid of the wild American hops alone rendered possible the production of a sufficient quantity for the first physiological experiments. The concentration of English beer, strongly charged with American hops, proved that this kind of hops contains a narcotic principle, the condensed beer possessing an undeniable, although mild, narcotic property. By boiling large quantities of American hops with wort, brewed after the English system, and condensing the extract in the vacuum, concentrated solutions of the new alkaloid were obtained, but its isolation still failed. This at last was realised by boiling under high pressure large quantities of wild American hops with a pure slightly acidified solution of grape-sugar. This solution was filtered through asbestos, and condensed in a vacuum at a low temperature; and from it the alkaloid, which is but slightly soluble in water, was extracted. Very large quantities of hops were required for the preparation of the first 100 grammes (3J ounces) of pure hopein, which are now serving for the therapeutic experiments still continuing. Detailed reports are promised by the discoverers.
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The Dublin Journal of Medical Science, October 1, 1885, Pages 354-355
PERISCOPE.
HOPEIN.
This alkaloid, which appears to be different from the lupulin of Griessmayer, is described by W. T. Smith of London, (Deutsch. med.Zeitg.), who refers to previous investigations by Williamson and Springmiihl, who gave it the name of hopein. It is said to be most abundant in the American wild hop. It occurs as a white crystalline powder, or in the form of needles a third of an inch long. It is very sparingly soluble in water, but dissolves freely in alcohol, the solution having the most intense bitter taste and a pronounced smell of hops. Chemically, it bears a close resemblance to morphin. In its physiological action it is a pure narcotic, even fatal doses producing no irritant effect; but it contracts the pupil, raises the temperature, and increases the frequency of the pulse at first, but afterward diminishes it. The deep sleep which it induces is apt to be preceded and followed by peculiar hazy hallucinations. The author has used it as a hypnotic, in doses ranging from one-third to six-tenths of a grain for adults, and in his own person he found that three-quarters of a grain produced symptoms of poisoning. He finds that the dose does not have to be increased on account of the system becoming habituated to the drug. He thinks that the "toxic dose" is not much above a grain and a half for adults, and not over nine-tenths of a grain for children.—N. Y. Med. Jour., August 15, 1885.
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Chemist and Druggist, January 15, 1886, Page 55
Hopeine
Dr. W. Williamson has given this name to a substance recently discovered by himself and Mr. Springmuehl, and consisting of the narcotic alkaloid of Hamulus lupulus, L., or the active principle of hops. The experiments made thus far would seem to point to hopeine as destined to play an important part in medicine, especially as an antispasmodic and a sedative in nervous diseases and affections of the brain. Indeed, Dr. Williamson claims for hopeine that it seems to unite the qualities of quinine and morphine, and possesses the properties of opiates without having, so far as has been ascertained, any of the drawbacks of these substances.
The wild American hops are the only variety of Strobuli humili from which it has been found practicable to extract hopeine, which alkaloid they contain to the extent of about 0.15 per cent, on an average, whereas English hops only give 0.05 per cent, of pure hopeine crystals, and the German variety did not contain a percentage at all sufficient to admit of its employment.
At present chemical experiments on hopeine are still in progress, and the formula for the substance has not yet been discovered.
Pure hopeine appears in brilliant white needles about 1 cm. long, or as a crystalline white powder, a sample of which latter variety has been submitted to us by the Concentrated Produce Company, of 10 Camomile Street, E.C., who represent the patentees.
This powder has the characteristic smell of hops: it is scarcely soluble in water (according to one authority 800 parts of water at 15° C. are required for its solution), but it dissolves in 50 parts of alcohol at 15° C, communicating to the solution an intensely bitter taste.
The following is the modus operandi for obtaining hopeine from wild American hops:—-The hops are strongly compressed and placed in a large copper cauldron, tinned inside, a 16-per-cent. solution of glucose and a little acetic acid being added, and the mixture left standing for about twenty-four hours, the solution completely permeating and covering the compressed hops. Fermentation is prevented by the hops themselves. The next stage of the process is to boil the hops with the solution under pressure for six hours, then to remove the liquid and to place the hops in a hydraulic press. The solution of glucose, which, during the process has absorbed the active principles of the hops, among them the hopeine, is then filtered through carbon and treated in vacuum-pans until the sugar has crystallised.
The hopeine is now extracted from the residue in an impure state by means of alcohol, the solution filtered and evaporated. After evaporation the substance is treated alternately with ether and with weak alkali water to remove the impurities, and finally the pure alkaloid is extracted by repeated solution and re-crystallisation from alcohol. It may be interesting to mention that the circumstances which led to the investigations concerning the alkaloid arose from the discovery that English beer which contained a large proportion of hops after concentration in a vacuum acted as a powerful narcotic. The experimenters at first endeavoured to obtain hopeine directly by subjecting hops to a treatment with alcohol; but this did not succeed because the alcohol extracted several other substances at the same time, and no isolation was afterwards possible.
The manufacture of hopeine is still in its infancy, and of a difficult and expensive nature, 1,000 to 2,000 lbs. of hops yielding only 1 lb. of hopeine. and until progress has been made in the direction of simplification the price of the alkaloid is not likely to be sensibly reduced. The hops after treatment do not, however, become absolutely valueless for brewing purposes, nor does the sugar used in the process.
Unsuccessful experiments have been made to obtain hopeine from lupuline.
Its extremely bitter taste renders hopeine difficult to administer unless in a disguised form, condensed beer, port wine, or sherry being best employed for this purpose.
The alkaloid acts with very strong effect, especially upon, children, and should be administered with great caution.
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February 15, 1886, Pages 78-79
HOPEINE AND MORPHINE.
In December we described the properties of "Hopeine," a substance reported to have been recently discovered by Dr. Williamson and Mr. Springmuehl, and said to be the active principle of hops. During the past month this hopeine has been investigated by several French chemists and physicians, who all came to the conclusion that it is either morphine or an alkaloid exactly similar to morphine. This was first stated publicly at a meeting of the Academy of Medicine on January 27, by Dr. Dujardin-Beaumetz, who based his assertions on some experiments which had been made by M. Bardet for the firm of Adrian & Co. M. Bardet's experiments are given in full in a French journal called Nouceaux Remedes (February 1, 1886), which, we believe, is in some way connected with the house named. In that journal is published, first, a translation of the article in Tne Chemist And Druggist for December; then a history of the steps taken by M. Adrian to procure some samples of the alkaloid for Dr. Dujardin-Beaumetz; then the analyses; and, finally, the inevitable homily on the depravity of all druggists outside France.
Messrs. Adrian & Co. obtained their hopeine first throngh the firm of Thomas Christy & Co. here. This, M. Bardet reports, possessed a pronounced sweetish odour, curiously like that of wintergreen oil, and an atom placed on the tongue, besides having a bitter and nauseous taste, left a pronounced burning sensation, like the action of essential oik. These properties arousing his suspicion, Dr. Bardet dissolved part of the sample in alcohol, which dissolved it easily, and, on further analysis, he became convinced it was morphine he was dealing with.
In order to be quite certain Dr. Bardet asked M. Adrian to procure him some more hopeine, but from different British firms, in order to have, as he expressed it, "samples of different marks."
While waiting for the arrival of these samples another Parisian chemist, M. A. Petit, who had also conduct^ experiments on hopeine, informed Messrs. Bardet and Adrian that he had found it to produce exactly the same reactions as morphine, and M. Adrian was further surprised by being offered by agents of different London houses large quantities of hopeine, which article had before been extremely scarce.
The second lot of samples arrived from London in sealed bottles, some from Christy and others from the original manufacturers, the Concentrated Produce Company, and upon these being opened that of Christy was found to possess the same odour of wintergreen oil as the first, while that of the Company smelt strongly of hops. In other respects the two had the same properties, and were subjected to a series of tests which were held to prove that hopeine possesses the same reactions as morphine, and is, in fact, identical with morphine; that, therefore, either hops contain morphine—-which is difficult to believe, but remarkable if true—-or that the product sold as hopeine by English druggists is morphine scented with an essential oil.
Messrs. Christy &. Co. have very freely laid before us all the particulars of their transactions in the matter. Of course their part in the affair has been simply that of merchants, although they must accept the comments of the French press smilingly, because they followed the frequent practice of substituting their label for that of the original agents.
Messrs. Christy & Co. inform us that they received a letter, dated January 26, in which M. Adrian relates the analysis of the hopeine, and adds that, Christy having furnished him with a mixture of morphine and some aromatic substance for hopeine, he refuses to pay for the several lots he has bought from him. Upon receipt of this letter Mr. Christy communica>ed with the Concentrated Produce Company, and gave a sample of hopeine to Wigner & Harland for analysis. When our representative called Mr. Christy showed him a letter from the Concentrated Produce Company, dated February 2, in which they guarantee that the article supplied by them was in every respect the same as was supplied direct by them to M. Adrian, and that, as stated in their circular, hopeine is prepared exclusively from hops. "I was quite staggered," Mr. Christy went on to say, 'by the article in the Nouceaux Remedes, and desire nothing better than to clear up the matter entirely. But, even if the French are right in their analysis, that would not justify the personal attack upon me and other English druggists, who simply supply goods ordered from us as sent out by the manufacturers and who can take no responsibility as to the properties of goods. It seems that this hopeine was brought out some years ago under the name of ' Hoppein,' but was given up. As to the present product, I understand that Mr. E. Merck, of Darmstadt, has the exclusive sale of it on the Continent, and that M. Adrian, having ordered a parcel from the Concentrated Produce Company, they supplied him, but he received the invoice from Merck. The article has been sold largely in Germany, where many experiments have been made with it, and from there we have heard no complaints. However, besides having given some hopeine to Wigner & Harland for analysis, I have asked the Company to get a consignment of the original wild hops from America, which will be analysed here, and the matter settled once and for all."
Our representative then called upon Messrs. J. W. Drysdale & Co., druggists, of 4 Bury Street, St. Mary Axe, who have also supplied hopeine to a French house, and who made substantially the same statement as Mr. Christy. They were surprised, they said, to receive from their correspondent a letter saying that the hopeine and chlorhydrate of hopeine supplied by them were nothing but morphine and chlorhydrate of morphine, and adding that the parcel was at their disposal, and would not be paid for. "On prononce tout bas," said their correspondent, "le mot de vol!'
Mr. Drysdale is, of course, equally anxious to have the matter elucidated, and has received from the Concentrated Produce Company the same assurances as Mr. Christy.
In opposition to the statements published by the French chemists we have received a long statement in German, signed by Dr. G. V. Weissenfeld, M.D., Ph.D., entitled "Hopeine and Morphine.' From this document we extract the salient points:—
"While several well-known chemists have pointed out the great resemblance existing between morphine and hopeine, it is clearly shown by the investigations of Smith, Williamson, and Roberts that these two alkaloids are not identical.
"To point, like Bardet, to the colour tests as proof of the identity of the two alkaloids is as unjustifiable as it would be to maintain that atropin, hyoscyamine, and datnrin are identical because they show similar points of resemblance.
"It may be, of course, that morphium is actually present in Humulus, L., as well as in the poppy, just as caffeine is found in Coffea arab., Thea chinensis, Paullinia sorbilis, &c.
"Some of Bardet's reactions are not even characteristic of morphine, and if the crystals obtained by sublimation are examined under the microscope the difference between hopeine and morphine will at once become apparent, and the same result is obtained by exposing a drop of the alcoholic solution to free evaporation.
"The point of solution of hopeine is under 100° C, that of morphine over 120° C. The point of sublimation is under 130° C. for hopeine, over 160° C. for morphine. The smell of hops does not properly belong to hopeine, but is caused by traces of a decomposition product of the alkaloid. The characteristic smell of hops, although expelled from hops by the drying process, may be revived by heating it with sulphuric acid.
"The sediment caused in concentrated solutions by tannic acid is soluble in morphine by the addition of a drop of hydrochloric acid, and not soluble in hopeine.
"There are also great physiological differences between morphine and hopeine, especially in their action on the pupil. The former always causing myosis, while hopeine, if applied to the eye of a cat in small doses, causes dilatation; in large doses the mydriatic action on the human eye is also apparent. Crystallised hopeine only should be used in experiments."
Since writing the above we have heard that Messrs. Wigner & Harland's analysis, as far as it has gone, indicates no chemical difference between hopeine and morphine. It is stated, however, that another English chemist having made some preliminary experiments does not hold the same opinion; and it is fair to the Concentrated Produce Company to say that they have undertaken to supply to Mr. Christy and M. Petit, as independent authorities, sufficient quantities of the American wild hops to enable them to test their process for extracting the alkaloid. Hopeine, they say, is with them a by-product, their chief manufacture being a condensed beer for which they use the American wild hops.
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Couldn't find the Pharmaceutical Journal for 1886 online. Here's a reprint of Paul's article.
Pharmaceutical Record (New York), May 1, 1886, Page 139
NOTE ON A SAMPLE OF "HOPEINE."
By B. H. Paul, Ph.d.
Read at at evening meeting of the Pharmaceutical Society, Wednesday, April 14.
Some weeks ago, when a sample of "hopeine" was shown at one of the evening meetings of the Society, I gave a short account of a few results that I had obtained in examining the substance that has been spoken of under this name in some scientific journals, and has been described in advertisements as a narcotic alkaloid obtained from hops. Hitherto, so far as the chemistry of hops has been studied, there has not been any recognition of the presence of alkaloidal substances either in any part of the plant itself or in the lupulin that is separated from the strobiles, and any narcotic property appertaining to hops has been ascribed to other substances. On the occasion I refer to I pointed out that the alkaloid to which the name of "hopeine" had been given presented remarkable analogies to morphine. The quantity then at my command was very small, but the results obtained with the tests that I applied led me to the opinion that for the most part this substance was indistinguishable from morphine. In this respect my observations agreed with those which had been made in France. There was, however, some reason to suspect that "hopeine" was not in all instances the same thing, and therefore in order to be certain that there was no mistake about the material operated upon I applied to the vendors of this article requesting them to supply me with an authentic sample. I received from them two small tubes each containing about half a gram of substance in a crystalline state. This I submitted to examination as before, and I found it to be so closely analogous to morphine, that, if not identical with it, there was no possibility of distinguishing one from the other in comparative trials. The only particular in which I found any difference was, as I mentioned before, that in dissolving "hopeine" with caustic potash solution, though the greater part of it behaved in the same manner as morphine, and was dissolved readily, there was always some slight residue that remained undissolved; a very small proportion, but enough to be distinctly recognizable even when operating upon a centigram. This undissolved portion collected at the bottom of the test-tube, and after the lapse of several days it was observed that it gradually disappeared. Since it had been stated in the account given of hopeine that it possessed mydriatic properties, and that when applied to the eye it decidedly dilated the pupil, it occurred to me that this character might be due to some admixture of atropine. In any case no such effect had ever been observed with morphine, and as I was strongly impressed with the opinion that the greater part of this material was morphine I was at first inclined to suspect that the portion undissolved by caustic potash might consist of atropine. In my endeavor to arrive at a determination of that point I was, however, unable to satisfy myself of the presence of this alkaloid, inasmuch as the recognition of small quantities of atropine is exceedingly difficult. The entire quantity of the material I was operating upon weighed altogether only about half a gram, and if the portion undissolved was really atropine it could not have amounted to more than a milligram.
After I had mentioned this matter I incidentally learned from Mr. Wink that he had met with samples of "hopeine" which were distinctly different from one another. In one instance a sample had been found to present characters very different from other samples. In the first place it melted in a water-bath long before the temperature of 212° F. was reached, and in that respect it was obviously quite distinct from morphine, as well as from other samples of "hopeine." He was kind enough at my request to send me a small tube containing about half a gram of this sample, and upon examination I found that the melting point was considerably below 194° F. After being melted it presented the appearance partly of an oily mass, which solidified on cooling, while part of it appeared to remain unmelted. Still pursuing the idea that atropine might be present, 1 endeavored to separate this fusible portion by means of the solvents which are best suited for dissolving atropine,—-amongst others chloroform,—-and I found that on treating the sample of hopeine obtained from Mr. Wink with chloroform a considerable proportion of it was dissolved. The undissolved portion of it was first examined and found to possess all the characters of morphine. The soluble portion was converted into hydrochorate and the solution evaporated down to a very small bulk. Upon comparing the residue with that obtained from a similar solution of atropine hydrochlorate I found that there was a considerable difference. The atropine hydrochlorate was never obtained in a crystalline form at all, but only as a distinctly gummy mass without any sign of crystallization. The substance soluble in chloroform which was separated from Mr. Wink's sample of hopeine, however, gave a decidedly crystalline hydrochlorate and this salt was deliquescent. I found that this alkaloid soluble in chloroform, amounting to about one third of the sample—about 30 per cent—was really cocaine. On applying to it the ordinary chemical tests it corresponded in every respect with a good sample of cocaine. It also presented the physiological characters of cocaine, producing numbness of the tongue. When boiled with water it was converted into the fine crystallizable substance that is a product of the decomposition of cocaine in that way. Then by boiling for two or three minutes with a small quantity of caustic potash it was decomposed, with formation of benzoic acid, and on addition of hydrochloric acid benzoic acid was separated. This test for cocaine is under certain limitations decidedly characteristic. It requires to be delicately managed, with due regard to the solubility of benzoic acid in water, especially when operating upon a very small quantity. Care must also be taken not to use too much potash, otherwise the crystallization of the benzoic acid may be rendered obscure.
The general result that I have arrived at is that the greater part of the substance called "hopeine" is really morphine, and that if it be not morphine obtained from opium, it is so like morphine derived from that source as to be indistinguishable from it. Therefore if the account given of it be correct, we must suppose that hops, as well as opium, contain morphine. The trials that have been made with hops grown in this country and in other parts of Europe have not given any result showing the presence of morphine. Thus, for instance, Messrs. Gehe, of Dresden, have tried a large quantity of hops for the purpose of extracting from them any alkaloid to be obtained. They failed entirely, and have obtained nothing of the kind.
It is stated, however, that hopeine is obtained from a peculiar kind of hop—-a wild variety growing in Central America. For the further elucidation of the matter in this respect it would therefore be requisite that a large quantity of these wild hops of Central America should be brought over here and submitted to trial, and probably it will be some time before this will be done.
Within the last few hours I have had some conversation with Mr. Gerrard and I have heard that he has also met with a sample of hopeine that was even more remarkable than the one which I have already described as containing one-third of its weight of cocaine. The sample which he has examined was obtained through a wholesale house in London, directly from the vendors, and according to Mr. Gerrard's account he has separated it into one-fourth of a substance which he finds to be identical with morphine, and three-fourths of a substance which is soluble in chloroform. He has very kindly handed this over to me this morning, and in the course of the afternoon I have examined it and I find that it is cocaine. The alkaloid alleged to be produced from hops is therefore peculiar in being separable into one portion that is certainly identical with morphine, and another portion that is identical with an alkaloid that occurs in a plant belonging to a natural order very different from those to which the poppy and hop belong respectively. Hence it appears that we have to adopt one of two alternatives. Either there is in the wild hop of Central America a very remarkable association of two alkaloids known to occur in two extremely different plants, or we have a case of an article improperly put forward as a substance of natural origin, though really a fictitious mixture. It is difficult to imagine how such a proceeding could have been attempted. We can understand well enough quack nostrums being put before the public with wonderful accounts of their virtues. It is intelligible that a new narcotic preparation of that kind might be introduced under a fancy name and at a high price; but the attempt to introduce upon a pseudo-scientific basis an article that is only a mixture of two well-known substances is, I may say, a piece of foolish impudence that almost passes belief.—Reprinted from the Pharmaceutical Journal.
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Some hopeine related correspondence which includes a mention of a Brooklyn connection for for the Concentrated Produce Company.
American Druggist, July 1886, Pages 136-137
Hopeine.
Sir :—Our attention has been directed to an article in your valuable medium on the subject of hopeine, and we should feel obliged if you would allow us to take exception to the statement that we were makers of hopeine, for if not contradicted at once, we should be placed in a false position both in America and Europe. Our connection with hopeine was inevitable, on account of the leading part we have always taken in the introduction and importation of new drugs and remedies; but not being ourselves manufacturers of any pharmaceutical preparations, we cannot hold ourselves responsible for their composition. When a new drug or preparation is brought on the market, we are at once called upon to supply it, and hopeine, so soon as it was advertised by the sole manufacturers. The Concentrated Produce Co., Limited, of London and Brooklyn, who by a letter to us dated February 2d, 1886, take the entire responsibility of their statements and of the preparation known as hopeine, it was oraered from us.
Our position and action in this matter has been fully explained by us to our friends, Mr. F. Stearns, Detroit: Prof. Lloyd, of Cincinnati, etc., and we have received great assistance from Professors F. Spencer Baird and Asa Gray, in collecting such information as has enabled us to obtain through Mr. J. W. Colcord, of Lynn, a supply of American wild hops, to have the question of their yield of the alkaline hopeine clearly defined. We remain, sir, yours truly,
Thos. Christy & Co.
London, June 1st, 1880.
(The above communication is accompanied by the following circular, which should be read in connection with it.— Ed. Amer. Druggist.J
10, Camomile street,
London, E. C, Feb. 2d, 1886.
Messrs. Thos. Christ if & Co., 155, Fenchurch Street, E. C.
Dear Sirs:—In reply to your inquiry, we guarantee that the hopeine supplied to you on 8th Dec, 12th Dec, and 21st Dec, 1885, and 19th Jan., and 21st Jan., 1886, was similar in every respect to the article we supply to our other customers, including Messrs. Adrian & Co., of Paris; and that, as stated in our circulars, hopeine is prepared exclusively from hops.
We are, dear sirs, yours truly.
Concentrated Produce Co.,
W. Wild. Springmuhl.
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Eh, it's just going to get worse.
Springmuhl's Concentrated Produce Company reported the discovery of a new narcotic, hopein or hopeine, derived from wild American hops. This discovery was the result of attempts to produce condensed beer. Independent analysts determined that samples of hopeine consisted of morphine or a mixture of morphine and cocaine. B. H. Paul of the Pharmaceutical Journal wrote: "It is intelligible that a new narcotic preparation of that kind might be introduced under a fancy name and at a high price; but the attempt to introduce upon a pseudo-scientific basis an article that is only a mixture of two well-known substances is, I may say, a piece of foolish impudence that almost passes belief."
The London Medical Record, August 15, 1885, Page 341
Hopein, the Narcotic Principle of Hops.—-An article on this subject appears in Der Fortschritt, June 20, 1885 [page 252]. It has long been supposed that hops contain a narcotic principle, the isolation of which however failed, until W. Williamson and Springmuehl first succeeded in obtaining from American hops a new alkaloid, hopein, of eminently narcotic properties, barely inferior in power to morphia, without, however, the objectionable subsequent effects of the latter. The experiments connected with concentration in vacuum of strongly hopped English beer and the brewing of condensed beer, lead to the conviction that certain qualities of hops contain small quantities of a narcotic alkaloid, in its properties closely related to morphia. Just as only certain kinds of poppies grown in particular climates yield a satisfactory quantity of morphia, so also the larger or lesser proportion of the narcotic principle of the hops vary according to the place and 'he manner of cultivation of this plant; whereas German hops possess only traces of hopein, the richness in this alkaloid of the wild American hops alone rendered possible the production of a sufficient quantity for the first physiological experiments. The concentration of English beer, strongly charged with American hops, proved that this kind of hops contains a narcotic principle, the condensed beer possessing an undeniable, although mild, narcotic property. By boiling large quantities of American hops with wort, brewed after the English system, and condensing the extract in the vacuum, concentrated solutions of the new alkaloid were obtained, but its isolation still failed. This at last was realised by boiling under high pressure large quantities of wild American hops with a pure slightly acidified solution of grape-sugar. This solution was filtered through asbestos, and condensed in a vacuum at a low temperature; and from it the alkaloid, which is but slightly soluble in water, was extracted. Very large quantities of hops were required for the preparation of the first 100 grammes (3J ounces) of pure hopein, which are now serving for the therapeutic experiments still continuing. Detailed reports are promised by the discoverers.
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The Dublin Journal of Medical Science, October 1, 1885, Pages 354-355
PERISCOPE.
HOPEIN.
This alkaloid, which appears to be different from the lupulin of Griessmayer, is described by W. T. Smith of London, (Deutsch. med.Zeitg.), who refers to previous investigations by Williamson and Springmiihl, who gave it the name of hopein. It is said to be most abundant in the American wild hop. It occurs as a white crystalline powder, or in the form of needles a third of an inch long. It is very sparingly soluble in water, but dissolves freely in alcohol, the solution having the most intense bitter taste and a pronounced smell of hops. Chemically, it bears a close resemblance to morphin. In its physiological action it is a pure narcotic, even fatal doses producing no irritant effect; but it contracts the pupil, raises the temperature, and increases the frequency of the pulse at first, but afterward diminishes it. The deep sleep which it induces is apt to be preceded and followed by peculiar hazy hallucinations. The author has used it as a hypnotic, in doses ranging from one-third to six-tenths of a grain for adults, and in his own person he found that three-quarters of a grain produced symptoms of poisoning. He finds that the dose does not have to be increased on account of the system becoming habituated to the drug. He thinks that the "toxic dose" is not much above a grain and a half for adults, and not over nine-tenths of a grain for children.—N. Y. Med. Jour., August 15, 1885.
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Chemist and Druggist, January 15, 1886, Page 55
Hopeine
Dr. W. Williamson has given this name to a substance recently discovered by himself and Mr. Springmuehl, and consisting of the narcotic alkaloid of Hamulus lupulus, L., or the active principle of hops. The experiments made thus far would seem to point to hopeine as destined to play an important part in medicine, especially as an antispasmodic and a sedative in nervous diseases and affections of the brain. Indeed, Dr. Williamson claims for hopeine that it seems to unite the qualities of quinine and morphine, and possesses the properties of opiates without having, so far as has been ascertained, any of the drawbacks of these substances.
The wild American hops are the only variety of Strobuli humili from which it has been found practicable to extract hopeine, which alkaloid they contain to the extent of about 0.15 per cent, on an average, whereas English hops only give 0.05 per cent, of pure hopeine crystals, and the German variety did not contain a percentage at all sufficient to admit of its employment.
At present chemical experiments on hopeine are still in progress, and the formula for the substance has not yet been discovered.
Pure hopeine appears in brilliant white needles about 1 cm. long, or as a crystalline white powder, a sample of which latter variety has been submitted to us by the Concentrated Produce Company, of 10 Camomile Street, E.C., who represent the patentees.
This powder has the characteristic smell of hops: it is scarcely soluble in water (according to one authority 800 parts of water at 15° C. are required for its solution), but it dissolves in 50 parts of alcohol at 15° C, communicating to the solution an intensely bitter taste.
The following is the modus operandi for obtaining hopeine from wild American hops:—-The hops are strongly compressed and placed in a large copper cauldron, tinned inside, a 16-per-cent. solution of glucose and a little acetic acid being added, and the mixture left standing for about twenty-four hours, the solution completely permeating and covering the compressed hops. Fermentation is prevented by the hops themselves. The next stage of the process is to boil the hops with the solution under pressure for six hours, then to remove the liquid and to place the hops in a hydraulic press. The solution of glucose, which, during the process has absorbed the active principles of the hops, among them the hopeine, is then filtered through carbon and treated in vacuum-pans until the sugar has crystallised.
The hopeine is now extracted from the residue in an impure state by means of alcohol, the solution filtered and evaporated. After evaporation the substance is treated alternately with ether and with weak alkali water to remove the impurities, and finally the pure alkaloid is extracted by repeated solution and re-crystallisation from alcohol. It may be interesting to mention that the circumstances which led to the investigations concerning the alkaloid arose from the discovery that English beer which contained a large proportion of hops after concentration in a vacuum acted as a powerful narcotic. The experimenters at first endeavoured to obtain hopeine directly by subjecting hops to a treatment with alcohol; but this did not succeed because the alcohol extracted several other substances at the same time, and no isolation was afterwards possible.
The manufacture of hopeine is still in its infancy, and of a difficult and expensive nature, 1,000 to 2,000 lbs. of hops yielding only 1 lb. of hopeine. and until progress has been made in the direction of simplification the price of the alkaloid is not likely to be sensibly reduced. The hops after treatment do not, however, become absolutely valueless for brewing purposes, nor does the sugar used in the process.
Unsuccessful experiments have been made to obtain hopeine from lupuline.
Its extremely bitter taste renders hopeine difficult to administer unless in a disguised form, condensed beer, port wine, or sherry being best employed for this purpose.
The alkaloid acts with very strong effect, especially upon, children, and should be administered with great caution.
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February 15, 1886, Pages 78-79
HOPEINE AND MORPHINE.
In December we described the properties of "Hopeine," a substance reported to have been recently discovered by Dr. Williamson and Mr. Springmuehl, and said to be the active principle of hops. During the past month this hopeine has been investigated by several French chemists and physicians, who all came to the conclusion that it is either morphine or an alkaloid exactly similar to morphine. This was first stated publicly at a meeting of the Academy of Medicine on January 27, by Dr. Dujardin-Beaumetz, who based his assertions on some experiments which had been made by M. Bardet for the firm of Adrian & Co. M. Bardet's experiments are given in full in a French journal called Nouceaux Remedes (February 1, 1886), which, we believe, is in some way connected with the house named. In that journal is published, first, a translation of the article in Tne Chemist And Druggist for December; then a history of the steps taken by M. Adrian to procure some samples of the alkaloid for Dr. Dujardin-Beaumetz; then the analyses; and, finally, the inevitable homily on the depravity of all druggists outside France.
Messrs. Adrian & Co. obtained their hopeine first throngh the firm of Thomas Christy & Co. here. This, M. Bardet reports, possessed a pronounced sweetish odour, curiously like that of wintergreen oil, and an atom placed on the tongue, besides having a bitter and nauseous taste, left a pronounced burning sensation, like the action of essential oik. These properties arousing his suspicion, Dr. Bardet dissolved part of the sample in alcohol, which dissolved it easily, and, on further analysis, he became convinced it was morphine he was dealing with.
In order to be quite certain Dr. Bardet asked M. Adrian to procure him some more hopeine, but from different British firms, in order to have, as he expressed it, "samples of different marks."
While waiting for the arrival of these samples another Parisian chemist, M. A. Petit, who had also conduct^ experiments on hopeine, informed Messrs. Bardet and Adrian that he had found it to produce exactly the same reactions as morphine, and M. Adrian was further surprised by being offered by agents of different London houses large quantities of hopeine, which article had before been extremely scarce.
The second lot of samples arrived from London in sealed bottles, some from Christy and others from the original manufacturers, the Concentrated Produce Company, and upon these being opened that of Christy was found to possess the same odour of wintergreen oil as the first, while that of the Company smelt strongly of hops. In other respects the two had the same properties, and were subjected to a series of tests which were held to prove that hopeine possesses the same reactions as morphine, and is, in fact, identical with morphine; that, therefore, either hops contain morphine—-which is difficult to believe, but remarkable if true—-or that the product sold as hopeine by English druggists is morphine scented with an essential oil.
Messrs. Christy &. Co. have very freely laid before us all the particulars of their transactions in the matter. Of course their part in the affair has been simply that of merchants, although they must accept the comments of the French press smilingly, because they followed the frequent practice of substituting their label for that of the original agents.
Messrs. Christy & Co. inform us that they received a letter, dated January 26, in which M. Adrian relates the analysis of the hopeine, and adds that, Christy having furnished him with a mixture of morphine and some aromatic substance for hopeine, he refuses to pay for the several lots he has bought from him. Upon receipt of this letter Mr. Christy communica>ed with the Concentrated Produce Company, and gave a sample of hopeine to Wigner & Harland for analysis. When our representative called Mr. Christy showed him a letter from the Concentrated Produce Company, dated February 2, in which they guarantee that the article supplied by them was in every respect the same as was supplied direct by them to M. Adrian, and that, as stated in their circular, hopeine is prepared exclusively from hops. "I was quite staggered," Mr. Christy went on to say, 'by the article in the Nouceaux Remedes, and desire nothing better than to clear up the matter entirely. But, even if the French are right in their analysis, that would not justify the personal attack upon me and other English druggists, who simply supply goods ordered from us as sent out by the manufacturers and who can take no responsibility as to the properties of goods. It seems that this hopeine was brought out some years ago under the name of ' Hoppein,' but was given up. As to the present product, I understand that Mr. E. Merck, of Darmstadt, has the exclusive sale of it on the Continent, and that M. Adrian, having ordered a parcel from the Concentrated Produce Company, they supplied him, but he received the invoice from Merck. The article has been sold largely in Germany, where many experiments have been made with it, and from there we have heard no complaints. However, besides having given some hopeine to Wigner & Harland for analysis, I have asked the Company to get a consignment of the original wild hops from America, which will be analysed here, and the matter settled once and for all."
Our representative then called upon Messrs. J. W. Drysdale & Co., druggists, of 4 Bury Street, St. Mary Axe, who have also supplied hopeine to a French house, and who made substantially the same statement as Mr. Christy. They were surprised, they said, to receive from their correspondent a letter saying that the hopeine and chlorhydrate of hopeine supplied by them were nothing but morphine and chlorhydrate of morphine, and adding that the parcel was at their disposal, and would not be paid for. "On prononce tout bas," said their correspondent, "le mot de vol!'
Mr. Drysdale is, of course, equally anxious to have the matter elucidated, and has received from the Concentrated Produce Company the same assurances as Mr. Christy.
In opposition to the statements published by the French chemists we have received a long statement in German, signed by Dr. G. V. Weissenfeld, M.D., Ph.D., entitled "Hopeine and Morphine.' From this document we extract the salient points:—
"While several well-known chemists have pointed out the great resemblance existing between morphine and hopeine, it is clearly shown by the investigations of Smith, Williamson, and Roberts that these two alkaloids are not identical.
"To point, like Bardet, to the colour tests as proof of the identity of the two alkaloids is as unjustifiable as it would be to maintain that atropin, hyoscyamine, and datnrin are identical because they show similar points of resemblance.
"It may be, of course, that morphium is actually present in Humulus, L., as well as in the poppy, just as caffeine is found in Coffea arab., Thea chinensis, Paullinia sorbilis, &c.
"Some of Bardet's reactions are not even characteristic of morphine, and if the crystals obtained by sublimation are examined under the microscope the difference between hopeine and morphine will at once become apparent, and the same result is obtained by exposing a drop of the alcoholic solution to free evaporation.
"The point of solution of hopeine is under 100° C, that of morphine over 120° C. The point of sublimation is under 130° C. for hopeine, over 160° C. for morphine. The smell of hops does not properly belong to hopeine, but is caused by traces of a decomposition product of the alkaloid. The characteristic smell of hops, although expelled from hops by the drying process, may be revived by heating it with sulphuric acid.
"The sediment caused in concentrated solutions by tannic acid is soluble in morphine by the addition of a drop of hydrochloric acid, and not soluble in hopeine.
"There are also great physiological differences between morphine and hopeine, especially in their action on the pupil. The former always causing myosis, while hopeine, if applied to the eye of a cat in small doses, causes dilatation; in large doses the mydriatic action on the human eye is also apparent. Crystallised hopeine only should be used in experiments."
Since writing the above we have heard that Messrs. Wigner & Harland's analysis, as far as it has gone, indicates no chemical difference between hopeine and morphine. It is stated, however, that another English chemist having made some preliminary experiments does not hold the same opinion; and it is fair to the Concentrated Produce Company to say that they have undertaken to supply to Mr. Christy and M. Petit, as independent authorities, sufficient quantities of the American wild hops to enable them to test their process for extracting the alkaloid. Hopeine, they say, is with them a by-product, their chief manufacture being a condensed beer for which they use the American wild hops.
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Couldn't find the Pharmaceutical Journal for 1886 online. Here's a reprint of Paul's article.
Pharmaceutical Record (New York), May 1, 1886, Page 139
NOTE ON A SAMPLE OF "HOPEINE."
By B. H. Paul, Ph.d.
Read at at evening meeting of the Pharmaceutical Society, Wednesday, April 14.
Some weeks ago, when a sample of "hopeine" was shown at one of the evening meetings of the Society, I gave a short account of a few results that I had obtained in examining the substance that has been spoken of under this name in some scientific journals, and has been described in advertisements as a narcotic alkaloid obtained from hops. Hitherto, so far as the chemistry of hops has been studied, there has not been any recognition of the presence of alkaloidal substances either in any part of the plant itself or in the lupulin that is separated from the strobiles, and any narcotic property appertaining to hops has been ascribed to other substances. On the occasion I refer to I pointed out that the alkaloid to which the name of "hopeine" had been given presented remarkable analogies to morphine. The quantity then at my command was very small, but the results obtained with the tests that I applied led me to the opinion that for the most part this substance was indistinguishable from morphine. In this respect my observations agreed with those which had been made in France. There was, however, some reason to suspect that "hopeine" was not in all instances the same thing, and therefore in order to be certain that there was no mistake about the material operated upon I applied to the vendors of this article requesting them to supply me with an authentic sample. I received from them two small tubes each containing about half a gram of substance in a crystalline state. This I submitted to examination as before, and I found it to be so closely analogous to morphine, that, if not identical with it, there was no possibility of distinguishing one from the other in comparative trials. The only particular in which I found any difference was, as I mentioned before, that in dissolving "hopeine" with caustic potash solution, though the greater part of it behaved in the same manner as morphine, and was dissolved readily, there was always some slight residue that remained undissolved; a very small proportion, but enough to be distinctly recognizable even when operating upon a centigram. This undissolved portion collected at the bottom of the test-tube, and after the lapse of several days it was observed that it gradually disappeared. Since it had been stated in the account given of hopeine that it possessed mydriatic properties, and that when applied to the eye it decidedly dilated the pupil, it occurred to me that this character might be due to some admixture of atropine. In any case no such effect had ever been observed with morphine, and as I was strongly impressed with the opinion that the greater part of this material was morphine I was at first inclined to suspect that the portion undissolved by caustic potash might consist of atropine. In my endeavor to arrive at a determination of that point I was, however, unable to satisfy myself of the presence of this alkaloid, inasmuch as the recognition of small quantities of atropine is exceedingly difficult. The entire quantity of the material I was operating upon weighed altogether only about half a gram, and if the portion undissolved was really atropine it could not have amounted to more than a milligram.
After I had mentioned this matter I incidentally learned from Mr. Wink that he had met with samples of "hopeine" which were distinctly different from one another. In one instance a sample had been found to present characters very different from other samples. In the first place it melted in a water-bath long before the temperature of 212° F. was reached, and in that respect it was obviously quite distinct from morphine, as well as from other samples of "hopeine." He was kind enough at my request to send me a small tube containing about half a gram of this sample, and upon examination I found that the melting point was considerably below 194° F. After being melted it presented the appearance partly of an oily mass, which solidified on cooling, while part of it appeared to remain unmelted. Still pursuing the idea that atropine might be present, 1 endeavored to separate this fusible portion by means of the solvents which are best suited for dissolving atropine,—-amongst others chloroform,—-and I found that on treating the sample of hopeine obtained from Mr. Wink with chloroform a considerable proportion of it was dissolved. The undissolved portion of it was first examined and found to possess all the characters of morphine. The soluble portion was converted into hydrochorate and the solution evaporated down to a very small bulk. Upon comparing the residue with that obtained from a similar solution of atropine hydrochlorate I found that there was a considerable difference. The atropine hydrochlorate was never obtained in a crystalline form at all, but only as a distinctly gummy mass without any sign of crystallization. The substance soluble in chloroform which was separated from Mr. Wink's sample of hopeine, however, gave a decidedly crystalline hydrochlorate and this salt was deliquescent. I found that this alkaloid soluble in chloroform, amounting to about one third of the sample—about 30 per cent—was really cocaine. On applying to it the ordinary chemical tests it corresponded in every respect with a good sample of cocaine. It also presented the physiological characters of cocaine, producing numbness of the tongue. When boiled with water it was converted into the fine crystallizable substance that is a product of the decomposition of cocaine in that way. Then by boiling for two or three minutes with a small quantity of caustic potash it was decomposed, with formation of benzoic acid, and on addition of hydrochloric acid benzoic acid was separated. This test for cocaine is under certain limitations decidedly characteristic. It requires to be delicately managed, with due regard to the solubility of benzoic acid in water, especially when operating upon a very small quantity. Care must also be taken not to use too much potash, otherwise the crystallization of the benzoic acid may be rendered obscure.
The general result that I have arrived at is that the greater part of the substance called "hopeine" is really morphine, and that if it be not morphine obtained from opium, it is so like morphine derived from that source as to be indistinguishable from it. Therefore if the account given of it be correct, we must suppose that hops, as well as opium, contain morphine. The trials that have been made with hops grown in this country and in other parts of Europe have not given any result showing the presence of morphine. Thus, for instance, Messrs. Gehe, of Dresden, have tried a large quantity of hops for the purpose of extracting from them any alkaloid to be obtained. They failed entirely, and have obtained nothing of the kind.
It is stated, however, that hopeine is obtained from a peculiar kind of hop—-a wild variety growing in Central America. For the further elucidation of the matter in this respect it would therefore be requisite that a large quantity of these wild hops of Central America should be brought over here and submitted to trial, and probably it will be some time before this will be done.
Within the last few hours I have had some conversation with Mr. Gerrard and I have heard that he has also met with a sample of hopeine that was even more remarkable than the one which I have already described as containing one-third of its weight of cocaine. The sample which he has examined was obtained through a wholesale house in London, directly from the vendors, and according to Mr. Gerrard's account he has separated it into one-fourth of a substance which he finds to be identical with morphine, and three-fourths of a substance which is soluble in chloroform. He has very kindly handed this over to me this morning, and in the course of the afternoon I have examined it and I find that it is cocaine. The alkaloid alleged to be produced from hops is therefore peculiar in being separable into one portion that is certainly identical with morphine, and another portion that is identical with an alkaloid that occurs in a plant belonging to a natural order very different from those to which the poppy and hop belong respectively. Hence it appears that we have to adopt one of two alternatives. Either there is in the wild hop of Central America a very remarkable association of two alkaloids known to occur in two extremely different plants, or we have a case of an article improperly put forward as a substance of natural origin, though really a fictitious mixture. It is difficult to imagine how such a proceeding could have been attempted. We can understand well enough quack nostrums being put before the public with wonderful accounts of their virtues. It is intelligible that a new narcotic preparation of that kind might be introduced under a fancy name and at a high price; but the attempt to introduce upon a pseudo-scientific basis an article that is only a mixture of two well-known substances is, I may say, a piece of foolish impudence that almost passes belief.—Reprinted from the Pharmaceutical Journal.
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Some hopeine related correspondence which includes a mention of a Brooklyn connection for for the Concentrated Produce Company.
American Druggist, July 1886, Pages 136-137
Hopeine.
Sir :—Our attention has been directed to an article in your valuable medium on the subject of hopeine, and we should feel obliged if you would allow us to take exception to the statement that we were makers of hopeine, for if not contradicted at once, we should be placed in a false position both in America and Europe. Our connection with hopeine was inevitable, on account of the leading part we have always taken in the introduction and importation of new drugs and remedies; but not being ourselves manufacturers of any pharmaceutical preparations, we cannot hold ourselves responsible for their composition. When a new drug or preparation is brought on the market, we are at once called upon to supply it, and hopeine, so soon as it was advertised by the sole manufacturers. The Concentrated Produce Co., Limited, of London and Brooklyn, who by a letter to us dated February 2d, 1886, take the entire responsibility of their statements and of the preparation known as hopeine, it was oraered from us.
Our position and action in this matter has been fully explained by us to our friends, Mr. F. Stearns, Detroit: Prof. Lloyd, of Cincinnati, etc., and we have received great assistance from Professors F. Spencer Baird and Asa Gray, in collecting such information as has enabled us to obtain through Mr. J. W. Colcord, of Lynn, a supply of American wild hops, to have the question of their yield of the alkaline hopeine clearly defined. We remain, sir, yours truly,
Thos. Christy & Co.
London, June 1st, 1880.
(The above communication is accompanied by the following circular, which should be read in connection with it.— Ed. Amer. Druggist.J
10, Camomile street,
London, E. C, Feb. 2d, 1886.
Messrs. Thos. Christ if & Co., 155, Fenchurch Street, E. C.
Dear Sirs:—In reply to your inquiry, we guarantee that the hopeine supplied to you on 8th Dec, 12th Dec, and 21st Dec, 1885, and 19th Jan., and 21st Jan., 1886, was similar in every respect to the article we supply to our other customers, including Messrs. Adrian & Co., of Paris; and that, as stated in our circulars, hopeine is prepared exclusively from hops.
We are, dear sirs, yours truly.
Concentrated Produce Co.,
W. Wild. Springmuhl.
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