The history of sulbutiamine is closely tied to the study of thiamine in Japan. A deficiency of thiamine causes a nervous system disorder called beriberi. Until the twentieth century, beriberi was prevalent in Japan and other Asian countries due to the widespread dependence on white rice as a staple food. The relationship between beriberi and diet was first noted by a navy surgeon named Takaki Kanehiro. Additional work resulted in the discovery of thiamine, which was isolated in 1926 and synthesized in 1936. The establishment of a Vitamin B Research Committee in Japan led to additional scientific investigation into the properties of thiamine and its derivatives.
The first lipophilic thiamine derivative to be discovered was allithiamine, which was isolated from garlic (Allium sativum) in 1951. Allithiamine is an allyl disulfide derivative. After the discovery of allithiamine, several additional derivatives were synthesized with the hope that they would have better pharmacokinetic properties than thiamine. Thiamine is unable to diffuse across plasma membranes because it has a positively charged thiazole moiety. Instead, it must be transported across plasma membranes by high affinity carriers, and the rate of transport is low. Sulbutiamine overcomes the poor oral bioavailability of thiamine because it is highly lipophilic. It is not clear when sulbutiamine was first synthesized, but the earliest reference to it in the literature is from 1973.
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