Neurotoxic action of β-N-oxalyl-l-α,β-diaminopropionic acid

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The Isolation and Characterization of β-N-Oxalyl-L-α,β-Diaminopropionic Acid: A Neurotoxin from the Seeds of Lathyrus sativus

A neurotoxic compound has been isolated from the seeds of Lathyrus sativus in 0.5% yield and characterized as β-N-oxalyl-L-α,β-diaminopropionic acid. The compound is highly acidic in character and forms oxalic acid and diaminopropionic acid on acid hydrolysis. The compound has a specific rotation of -36.9° and has apparent pK values in the order of 1.95, 2.95, and 9.25, corresponding to the two carboxyl and one amino functions, respectively. The compound has been synthesized by reacting an aqueous methanolic solution of the copper complex of L-α,β-diaminopropionic acid prepared at pH 4.5-5.0 with dimethyl oxalate under controlled pH conditions and isolating the compound by chromatography on a Dowex 50-H+ column after precipitating the copper. The compound induced severe neurological symptoms in day-old chicks at the level of 20 mg/chick, but not in rats or mice. It also inhibited the growth of several microorganisms and of the insect larva Corcyra cephalonica Staint. L-Homoarginine had no neural action in chicks. It is suggested that the neurotoxic compound is species specific in its action and may be related to "neurolathyrism" associated with the human consumption of L. sativus seeds

Experimental neurolathyrism in monkeys [24]

Until now the cause of the relation between Lathyrus sativus and the spastic paraplegia, known as neurolathyrism, has been inferred purely on epidemiological grounds and neurotoxic manifestations with or without histopathological verification have not so far been obtained. The isolation and characterization of β-N-oxalyl-L-α,β-diaminopropionic acid (OX-Dapro), an unusual amino-acid, which was "neurotoxic" to 1 day old chicks have, however, been reported. We have found that intraperitoneal injection of this compound in adult chicks required a proportionately much larger dose to produce similar effects. An intraperitoneal or intravenous administration of this compound to adult rats at a level of 1 mg/g body weight or intraperitoneally in mice did not produce any symptoms, while administration of 25μg intracisternally was seen to produce convulsions. It was felt that this might be caused by an effective "blood-brain barrier" and thus we decided to investigate the effect of this compound when intrathecally injected into adult monkeys (Macaca radiata)