Role of Monocarboxylate Transporters in Drug Delivery to the Brain
Marilyn E. Morris.
Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate
and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only
the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter
family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter
and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and
is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of
their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may
play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the
transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics
has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will
be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the
brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including
their role in the treatment of malignant brain tumors.
Keywords: Monocarboxylate transporters, γ-hydroxybutyrate, brain, lactate.
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