Pyrithiamine (hydrobromide)

Pyrithiamine (hydrobromide) is an inhibitor of thiamine kinase and thiamine pyrophosphate kinase. Pyrithiamine (hydrobromide) competitively inhibits thiamine transport and reduces intracellular levels of thiamine and its phosphates. Pyrithiamine (hydrobromide) is used to study thiamine deficiency with polyneuritic symptoms and Wernicke's encephalopathy^[1][2]. In Vitro: Pyrithiamine (hydrobromide) (6.23-300 μg; 10-60 min) potently inhibits TPP synthesis by partially purified rat liver thiaminokinase in vitro, with a pyrithiamine:thiamine ratio of 1:1 causing ~31-35% inhibition and higher ratios causing near-complete inhibition^[1]. In Vivo: Pyrithiamine (hydrobromide) (623 μg; oral; daily; 1-64 days) alongside 100 μg thiamine rapidly reduces tissue TPP levels and impairs thiamine-dependent enzyme activity in pigeons, inducing thiamine deficiency that closely resembles that caused by thiamine withdrawal^[1].
Pyrithiamine (hydrobromide) (623 μg; oral; daily; 4 days) alongside 100 μg thiamine reduces tissue TPP levels more rapidly in pigeons than withholding thiamine, particularly in brain tissue^[1].
Pyrithiamine hydrobromide (0.1-0.5 mg/kg; i.p.; daily; up to 26 days) induces dose- and time-dependent reductions in brain Cho/NAA ratios in thiamine-deficient rats, with no significant effect on Cr/NAA ratios, and higher doses produce neurotoxic signs more rapidly^[2].