Sulbutiamine - Mechanism of Action

Mechanism of Action

Sulbutiamine is a lipophilic molecule that crosses the blood–brain barrier more easily than thiamine. Its metabolism in the brain leads to an increase in the levels of thiamine and thiamine phosphate esters. While the exact mechanism of action of sulbutiamine is unknown, it is thought to occur through the upregulation of the reticular activating system, which is the center of arousal and motivation in the brain. The administration of sulbutiamine potentiates cholinergic activity in the hippocampus. It also potentiates glutamatergic activity in the prefrontal cortex through a reduction in the density of kainate glutamate receptors, which may occur in response to a modulation of intrasynaptic glutamate. The facilitation of central glutamatergic transmission is a likely explanation for the ability of sulbutiamine to improve memory. In addition to its action on cholinergic and glutamatergic transmission, the administration of sulbutiamine reduces the release of dopamine in the prefrontal cortex, which increases the density of D₁ dopamine receptors through a compensatory mechanism. The modulation of dopaminergic transmission may also contribute to the ability of sulbutiamine to improve memory. A possible explanation for the pharmacodynamics of sulbutiamine is the increased availability of thiamine triphosphate (ThTP). Although the full physiological role of ThTP is unknown, it is an integral component of synaptosomal membranes, participates in the phosphorylation of proteins, and activates chloride channels that have a large unit conductance. The activation of chloride channels by ThTP may be involved in the modulation of receptor binding.