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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Comparison of the effects of some thiamine analogues upon thiamine transport across the blood-brain barrier of the rat.

The flux of thiamine from the blood into the brain has been measured by a specially devised procedure in which a steady raised level of the vitamin, with or without radioactive labelling, was achieved rapidly and maintained steadily in the circulating blood plasma. This was done by a single rapid I.V. injection followed by a continuous injection given at a rate adjusted according to a pre-determined programme, so as to replace the injected material at the rate at which it had been found to leave the circulation in preliminary experiments. A series of four chemical analogues of thiamine were given to see how each affected the flux of thiamine into the brain and the findings are compared with those for a fifth analogue studied in previous work. Pyrithiamine, thiamine disulphide and acetylthiamine, like amprolium, inhibited thiamine transport across the blood-brain barrier. Kinetic analysis shows that they compete mainly for the saturable component of thiamine flux across the blood-brain barrier, with only a slight inhibition of the non-saturable component, most clearly seen with pyrithiamine. Oxythiamine, despite its close chemical similarity to thiamine did not have any significant effect upon the flux of the vitamin into the brain. These findings help to explain the efficacy of pyrithiamine administration, especially in conjunction with a thiamine-deficient diet, in rapidly producing central neurological signs of deficiency.[1]


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