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April 1960

Experimental Myelopathy Produced with a Pyrimidine Analogue

AMA Arch Neurol. 1960;2(4):463-475. doi:10.1001/archneur.1960.03840100101014

Pyrimidine nucleotides are precursors of nucleic acids; several are also known to be co-enzymes in carbohydrate and phospholipid metabolism.1 We have attempted to assess the physiological and metabolic roles of pyrimidine nucleotides in the central nervous system by the intrathecal administration of pyrimidine antimetabolites. Neurological disturbances have been reported with the use of several such substances. 6-Azauracil, an analogue of uracil, causes confusional states, progressing to coma and diffuse high-voltage, slow waves in the EEG in man2,3; these effects are reversible. Massive doses of this analogue produce ataxia and similar EEG changes in rats.4 5-Hydroxyuridine and 5-aminouridine, analogues of uridine, produce transient somnolence and seizures in rats upon intraventricular injection.5

Orotic acid is an effective precursor of acid-soluble and nucleic acid pyrimidines in many organs,6 the central nervous system included.7,8 Therefore, 5-fluoro-orotic acid (FO), a structural analogue of orotic acid (Fig. 1) was