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R E F E R E N C E S .

(1) ACTON and CHOPEA Ind. ¿led. Gaz. 1922. LVIL 412.

(2) STOCKMAN . . Ed. Med. Journ. 1917. XIX. 277.

(3) DniXNG .. .. Jourtu Pharm. <fc Expt. Therap. 1920. XIV . 359.

(4) RiTTHAtrsBN .. .. Bar. d. Chem. Ges. 1876. IX 30 1 ; 1896. XXI X. 844.,

2108., 2653.; Journ. Prakt. Chem. (2) 1870. IL

336 ; 1873. VIL 374. ; 1881. XX IV . 202 ; 1884.

X X I X . 359.

(5) LBVENE an d SENIOB . t Journ. Biol. Chem. 1916. XXV. 607.

(6) BERTRAND .. .. CompL Bend. 1906. CXTJTI. 833, 970 ; 1909. CXL VII.

25 2 ; 1910, CL. 180 ; 1911. CLI, 325, 885.

(7) Dox and Y O D B E . . Journ. Am. Chem. Soc 1922. X L I V . 1145.

A PRELIMINARY NOTE ON LATHYRISM

BY

ALBERT HOWARD,

JOHN LIONEL SIMONSEN,

A ND

L. A. P. ANDERSON,

(A n investigation under the auspices oj the Indian Research

Fund A ssociation.)

[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 deter-mining 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 th e 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.2D

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858 A Preliminary Note on Lathyrism.

especially durin g th e monsoon. So far the results obtained have been

negative.

It was suggested by one of us (A. H.) th at the seeds of a weed,

apparently Vicia sativa L., * (known in N orth Bihar as akta) which

occurred in all the cultures raised from bazaar seed by Khesari obtained

from many localities in Ind ia where lathyri sm is common, should be

considered. A chemical exam ination revealed the presence of a base

or a mixtu re 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 t heir seeds w ill

be studied. The various un it species in Lathyrus sativus are also beingstudied.

The chemical constituents of Vicia sativa have already been

thoroughly investigated. Ritthausen(4 ) many years ago showed

tha t 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. Subsequ ently Levene and Senior(5) have shown tha t

divicine is identical with 2:5-diaminotetrahydropyrim id-4:6-dione. It

may also be mentioned th at Bertrand and his collaborators (6) have

isolated from Vicia sativa a cyanogene tic 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 barb ituric acids possess marke dly poisonous proper-

ties. 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, botan ical, and chemical experimen ts which are in

progress.

* After our work on Vicia sativa had commenced, we discovered th at Dr. Jahind ra

Nath Sen had independently come to the conclusion that the seeds of this weed were

probably connected with thè*çause of lathyr ism. Dr. Sen at onoe placed his unpublished

results and notes at our disposal, for which we tak e th is opp ortunity of expressing our

indebtedness. .