Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake.

Article Details

Citation

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
DrugTransporterKindOrganismPharmacological ActionActions
AcyclovirSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
DopamineSolute carrier family 22 member 1ProteinHumans
Unknown
Substrate
Details
VerapamilSolute carrier family 22 member 1ProteinHumans
Unknown
Inhibitor
Details
Drug Interactions
DrugsInteraction
Acetylcholine
Choline
The risk or severity of adverse effects can be increased when Choline is combined with Acetylcholine.
Acetylcholine
Nicotine
The risk or severity of adverse effects can be increased when Nicotine is combined with Acetylcholine.
Acetylcholine
Reserpine
The risk or severity of adverse effects can be increased when Reserpine is combined with Acetylcholine.
Acetylcholine
Nelfinavir
The risk or severity of adverse effects can be increased when Nelfinavir is combined with Acetylcholine.
Acetylcholine
Indinavir
The risk or severity of adverse effects can be increased when Indinavir is combined with Acetylcholine.
Acetylcholine
Nevirapine
The risk or severity of adverse effects can be increased when Nevirapine is combined with Acetylcholine.
Acetylcholine
Disopyramide
The risk or severity of adverse effects can be increased when Disopyramide is combined with Acetylcholine.
Acetylcholine
Codeine
The risk or severity of adverse effects can be increased when Codeine is combined with Acetylcholine.
Acetylcholine
Progesterone
The risk or severity of adverse effects can be increased when Progesterone is combined with Acetylcholine.
Acetylcholine
Prazosin
The risk or severity of adverse effects can be increased when Prazosin is combined with Acetylcholine.
Interactions
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