How can Levodopa cross the blood-brain barrier, while Dopamine cannot?

Exogenous Dopamine is unable to cross the tight junctions of the endothelial cells in the blood-brain barrier (BBB). Dopamine has no clinically significant endogenous transporter on the blood-brain barrier and is otherwise too polar of a molecule to move through the lipid membrane. Levodopa, however, utilizes a receptor on the BBB known as Large amino acid transporter (LAT)  which allows it to be transported across the blood-brain barrier and decarboxylated into Dopamine.

REFERENCES

  1. Tsuji A. Small Molecular Drug Transfer across the Blood-Brain Barrier via Carrier-Mediated Transport Systems. NeuroRx. 2005;2(1):54-62.
  2. Laterra J, Keep R, Betz LA, et al. Blood—Brain Barrier. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999.
  3. Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, Kanai Y, Naito M, Tsuruo T, Minato N, Shimohama S. The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res. 2000 Oct 6;879(1-2):115-21.
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Dr. C Humphreys

Internal Medicine

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Dr. C Humphreys

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