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A, Howard, J. L. Simonsen and L. A. P. Ander$on.\859


REFERENCES.
(1) ACTON and CHOPEA (2) STOCKMAN .. Ind. led. Gaz. 1922. LVIL 412. Ed. Med. Journ. 1917. XIX. 277.

(3) DniXNG (4) RiTTHAtrsBN

.. ..

(5) LBVENE and SENIOB (6) BERTRAND .. (7) Dox and YODBE

. . Jourtu Pharm. < f c Expt. Therap. 1920. XIV. 359. . . Bar. d. Chem. Ges. 1876. I X 301 ; 1896. XXIX. 844., 2108., 2653.; Journ. Prakt. Chem. (2) 1870. IL 336 ; 1873. VIL 374. ; 1881. XXIV. 202 ; 1884. XXIX. 359. . t Journ. Biol. Chem. 1916. XXV. 607. . . CompL Bend. 1906. CXTJTI. 833, 970 ; 1909. CXLVII. 252 ; 1910, CL. 180 ; 1911. CLI, 325, 885. . . Journ. Am. Chem. Soc 1922. XLIV. 1145.

A PRELIMINARY NOTE ON LATHYRISM


BY

ALBERT HOWARD, JOHN LIONEL SIMONSEN,


AND

L. A. P. ANDERSON,
(An investigation under the auspices oj the Indian Research Fund Association.)
[Received for publication, December 9, 1922.]

IN view of the recent publication by Acton and Chopra(l) of a paper, entitled " The Production and Pharmacological Action of Khesari Amine," it appears desirable to place on record a short preliminary note of an investigation which we have undertaken with the object of determining the cause of the disease known as lathyrism. According to Stockman(2) and Dilling(3), the grain of Khesari (Laihyrus sativus) contains an alkaloid possessing poisonous properties. Our first experiments therefore were made with the object of isolating an alkaloid from this seed. Very careful tests on different samples showed that, contrary to the statements of these investigators, the grain from L. sativm was quite free from any trace of alkaloid. In view of these results it occurred to us that possibly an alkaloid developed in the grain on storage*
* So far we have been unable to detect any difference in samples of grain stored under varying conditions, but the experimenta are not yet completed.

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A Preliminary Note on Lathyrism.

especially during the monsoon. So far the results obtained have been negative. It was suggested by one of us (A. H.) that the seeds of a weed, apparently Vicia sativa L., * (known in North Bihar as akta) which occurred in all the cultures raised from bazaar seed by Khesari obtained from many localities in India where lathyrism is common, should be considered. A chemical examination revealed the presence of a base or a mixture of bases which responded to the ordinary tests for alkaloids. Other leguminous weeds besides aleta occur in the khesari crop. These are being grown in pure culture and their seeds will be studied. The various unit species in Lathyrus sativus are also being studied. The chemical constituents of Vicia sativa have already been thoroughly investigated. Ritthausen(4) many years ago showed that it contained a base to which he gave the name vicine. He further showed that it was a glucoside yielding on acid hydrolysis a sugar and a new base divicine. Subsequently Levene and Senior(5) have shown that divicine is identical with 2:5-diaminotetrahydropyrimid-4:6-dione. It may also be mentioned that Bertrand and his collaborators (6) have isolated from Vicia sativa a cyanogenetic glucoside vicianin, which is closely related to amygdalin. It appeared to us possible that the base vicine, or its hydrolytic product divicine, might be physiologically active especially as it has been observed by Dox and Yoder(7) that somewhat closely related bodies, various alkyl benzyl barbituric acids possess markedly poisonous properties. A quantity of divicine hydrochloride has been prepared and is now being examined pharmacologically. In addition to vicine, the seeds occurring with L. sativus appear to contain other bases which are under investigation. We hope in a subsequent paper to describe in detail the various pharmacological, botanical, and chemical experiments which are in progress.
* After our work on Vicia sativa had commenced, we discovered that Dr. Jahindra Nath Sen had independently come to the conclusion that the seeds of this weed were probably connected with th*ause of lathyrism. Dr. Sen at onoe placed his unpublished results and notes at our disposal, for which we take this opportunity of expressing our indebtedness. .

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