To investigate the role of glutamic (Glu) and aspartic acid (Asp) in migraine, we measured the plasma amino acids in migraine patients with and without aura, between and during attacks, and compared the profiles with the plasma amino acid profiles of tension headache patients and healthy controls. Between attacks, migraineurs (notably with aura) had substantially higher plasma Glu and Asp levels than did controls and tension headache patients. In addition, patients with migraine without aura showed low plasma histidine levels. During migraine attacks, Glu (and to a lesser extent Asp) levels were even further increased. The results suggest a defective cellular reuptake mechanism for Glu and Asp in migraineurs, and we hypothesize a similar defect at the neuronal/glial cell level, predisposing the brain of migraineurs to develop spreading depression.

No abstract

L . Brandsma et al. / A n improved synthesis of the antithyroid factor DL-goitrinRed. Trav. Chim. Pays-Bas 107, 132-133 (1988) Goitrin' is the trivial name for 5-vinyloxazolidine-2-thion (6), a compound showing antithyroid activity' in several species of Brassicae and Cruciferae, including turnip, cabbage and rape. Both the racemic mixture of 6 and the naturally occurring L-isomer may cause simple goiter upon ingestion. The compound 6 has been obtained in a good yield by converting 1-amino-3-buten-2-01 (5) with aqueous alkali and carbon disulfide and subsequently treating the dithiocarbamate H,C= CH-CH(0H)-CH,NH(CS)SK with lead nitrate3. Reaction of butadiene 1 ,2-epoxide with aqueous ammonia gave 5 in 45% yield, in addition to its isomer, 2-amino-3-buten-1-01. The 1-isomer 5 was obtained from the mixture via fractional crystallization of the oxalates. The most serious draw-back of this synthesis, however, is the difficult accessibility of butadiene 1,2--epoxide. It is commercially available but the price is very high.Since, for toxicity studies, a large quantity of DL-goitrin was required, we developed an alternative synthesis for the key intermediate DL-1 -amino-3-buten-2-01 (5). In view of the good yield ( -70%) of DL-goitrin, obtained from this amino alcohol, our synthesis, depicted in the scheme below, may be considered as a formal synthesis of DL-goitrin. In our first attempts to prepare the hydroxy nitrile 2 we followed the original procedure4, which gave an impure product in a moderate yield. Distillative purification gave rise to extensive decomposition. Particularly the water, still present in the undistilled product, caused serious difficulties (sluggish and incomplete reaction, formation of intractable brown by-products) during the acid-catalysed protection of the OH function with ethyl vinyl ether. For these reasons, we developed a modified procedure for the hydroxy nitrile 2, consisting of addition of glacial acetic acid (excess) to a OH K C s N , CH,COOH

Using excess KCN and glacial AcOH the difficulties can be avoided arising from moisture in the synthesis of the cyanohydrin (IV).