Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake.
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Boxberger KH, Hagenbuch B, Lampe JN
Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake.
Drug Metab Dispos. 2014 Jun;42(6):990-5. doi: 10.1124/dmd.113.055095. Epub 2014 Mar 31.
- PubMed ID
- 24688079 [ View in PubMed]
- Abstract
The human organic cation transporter 1 (OCT1) is a polyspecific transporter involved in the uptake of positively charged and neutral small molecules in the liver. To date, few endogenous compounds have been identified as OCT1 substrates; more importantly, the effect of drugs on endogenous substrate transport has not been examined. In this study, we established monoamine neurotransmitters as substrates for OCT1, specifically characterizing serotonin transport in human embryonic kidney 293 cells. Kinetic analysis yielded a Km of 197 micomolar and a Vmax of 561 pmol/mg protein/minute for serotonin. Furthermore, we demonstrated that serotonin uptake was inhibited by diphenhydramine, fluoxetine, imatinib, and verapamil, with IC50 values in the low micromolar range. These results were recapitulated in primary human hepatocytes, suggesting that OCT1 plays a significant role in hepatic elimination of serotonin and that xenobiotics may alter the elimination of endogenous compounds as a result of interactions at the transporter level.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Acyclovir Solute carrier family 22 member 1 Protein Humans UnknownSubstrateInhibitorDetails Dopamine Solute carrier family 22 member 1 Protein Humans UnknownSubstrateDetails Verapamil Solute carrier family 22 member 1 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcetylcholineCholine The risk or severity of adverse effects can be increased when Choline is combined with Acetylcholine. AcetylcholineNicotine The risk or severity of adverse effects can be increased when Nicotine is combined with Acetylcholine. AcetylcholineReserpine The risk or severity of adverse effects can be increased when Reserpine is combined with Acetylcholine. AcetylcholineNelfinavir The risk or severity of adverse effects can be increased when Nelfinavir is combined with Acetylcholine. AcetylcholineIndinavir The risk or severity of adverse effects can be increased when Indinavir is combined with Acetylcholine.