Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2

Biopharm Drug Dispos. 2003 Nov;24(8):357-65. doi: 10.1002/bdd.371.


OCTN2 (SLC22A5), an organic cation/carnitine transporter, is widely distributed throughout the body, including the brain. In the present study, the involvement of OCTN2 in acetyl-L-carnitine (ALCAR) permeation across the blood-brain barrier (BBB) was examined using a microdialysis method in mouse. OCTN2 function was examined by comparison of wild-type mice with jvs mice, which express defective OCTN2 and are considered a model for primary systemic carnitine deficiency. Zero-net-flux method analysis indicated higher in vivo recovery of ALCAR and lower physiological ALCAR concentration in thalamus extracellular fluid (ECF) in jvs mice compared with wild-type mice. Externally added ALCAR showed significantly slower initial uptake across the BBB in jvs mouse. These results indicated that OCTN2 is functionally involved in ALCAR transfer across the BBB. Total radioactivity in ECF after i.v. administration of radiolabelled ALCAR remained constant for the rest of the experimental period. Accordingly, our results indicate that ALCAR is transported from blood to brain ECF by OCTN2 at least in part, and its concentration in brain ECF is regulated by other events such as protein binding and anabolic reactions in the brain, as well as by transport across the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / blood
  • Acetylcarnitine / pharmacokinetics*
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Injections, Intravenous
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Microdialysis
  • Organic Cation Transport Proteins*
  • Solute Carrier Family 22 Member 5
  • Time Factors
  • Tissue Distribution


  • Carrier Proteins
  • Membrane Proteins
  • Organic Cation Transport Proteins
  • SLC22A5 protein, human
  • Solute Carrier Family 22 Member 5
  • Acetylcarnitine