Hydrophilic anti-migraine triptans are substrates for OATP1A2, a transporter expressed at human blood-brain barrier

Xenobiotica. 2012 Sep;42(9):880-90. doi: 10.3109/00498254.2012.675455. Epub 2012 Apr 18.


OATP1A2 is expressed in the luminal membrane of human blood-brain barrier (BBB). The human tissue with the highest OATP1A2 mRNA expression is the brain. We have established a robust BacMam2-OATP1A2 transduced HEK293 system. Among the 36 central nervous system (CNS) marketed drugs tested, hydrophilic triptans, 5-HT(1B/1D) receptor agonists for the treatment of migraine attacks, were identified as OATP1A2 substrates. Kinetics (K(m) and V(max)) were determined for six marketed triptans. Structure-activity relationship (SAR) obtained from 18 triptan structural analogs revealed that the positively charged basic amine atom was essential for efficient OATP1A2-mediated triptan uptake and uptake rate was in the order of tertiary > secondary > primary. Preliminary quantitative SAR analysis of the triptan analogs demonstrated positive correlation between OATP1A2-mediated uptake rate and van der Waals volume (vdw_vol). OATP1A2 was specifically expressed on the apical side of MDCKII monolayer after BacMam2-OATP1A2 transduction and can facilitate transport of triptans across the MDCKII monolayer from apical to basolateral side. Involvement of OATP1A2 for brain penetration of triptans in human requires further investigation.

MeSH terms

  • Animals
  • Baculoviridae
  • Blood-Brain Barrier / metabolism*
  • Dogs
  • Genetic Vectors / genetics
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Madin Darby Canine Kidney Cells
  • Migraine Disorders / drug therapy*
  • Organic Anion Transporters / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Serotonin 5-HT1 Receptor Agonists / metabolism*
  • Serotonin 5-HT1 Receptor Agonists / therapeutic use
  • Structure-Activity Relationship
  • Tryptamines / metabolism*
  • Tryptamines / therapeutic use


  • Organic Anion Transporters
  • SLCO1A2 protein, human
  • Serotonin 5-HT1 Receptor Agonists
  • Tryptamines