+44-20-4587-4809
Veronique Michaud
Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM),
900 Rue St.-Denis, Room R08-480, Montreal, QC, H2X 0A9
Canada
Research Article
Effects of Tricyclic Compounds on the Transport of Anti-migraine Triptans through Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Author(s): Jennifer Lu, Alexia Grangeon, Fleur Gaudette, Jacques Turgeon and Veronique MichaudJennifer Lu, Alexia Grangeon, Fleur Gaudette, Jacques Turgeon and Veronique Michaud
OATP1A2 is a membrane drug-transporter expressed at the human blood-brain barrier (BBB) that may potentially mediate penetration of drugs in the brain. Triptans, hydrophilic antimigraine drugs, are substrates of OATP1A2. It is believed that triptans should cross the BBB to reach their site of action. Thus, OATP1A2 can limit brain penetration of triptans and may consequently influence their antimigraine drug action. We have previously demonstrated that compounds composed of a tricyclic ring with a short aliphatic amine chain, such as tricyclic antidepressants and carvedilol, inhibited OATP1A2-mediated rosuvastatin uptake. The main objective of this study was to determine whether triptans transport via OATP1A2 is affected by tricyclic compounds. First, we confirmed that triptans were substrates of OATP1A2 but not OATP2B1 using HEK293 stable cell lines. The tricyclic drugs evaluated were.. View More»