![]() Like most transporters in the SLC22A family, it is composed of 12 α-helical transmembrane domains (TMDs) with intracellular N- and C-termini ( Shu et al., 2003 Koepsell, 2013 Lozano et al., 2013). The human OCT1 protein has 554 amino acids. The human SLC22A1 gene encoding hOCT1 is located on chromosome 6q26 and consists of 11 exons and 10 introns ( Koehler et al., 1997). rOCT1 was cloned in 1994, and hOCT1 in 1997 by Koepsell group ( Grundemann et al., 1994 Gorboulev et al., 1997). Rat OCT1 (rOCT1) was the first cloned member of the SLC22A family. OCT1 is a member of the Solute Carrier (SLC) Family 22 responsible for the uptake of numerous organic cations, anions and zwitterions, across the plasma membrane ( Koepsell, 2013). 2 Molecular Cloning and Characterization of Organic Cation Transporter 1 Herein the physiological and pharmacological effects of OCT1 are briefly introduced, followed by a focused review on DDIs mediated by OCT1. Because OCT1 can also transport certain endogenous metabolites, its activity may also be of great significance to the maintenance of homeostasis in the body ( Nies et al., 2011b Lozano et al., 2013 Brosseau and Ramotar, 2019 Li et al., 2019). ![]() OCT1 function is thus closely related to pharmacotherapy of various diseases including cancer, cardiovascular and cerebrovascular diseases, digestive system diseases, substance addiction and CNS diseases. The disposition of more than 120 drugs has been related to the activity of OCTs including OCT1-3 ( Nies and Schwab, 2010). Approximately 40% of prescription medicines are organic cations ( Neuhoff et al., 2003 Koepsell, 2020). The human organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is highly expressed in the liver and possesses a broad substrate specificity ( Koepsell et al., 2003). Drug transporters exist in almost all organs of human body, mainly in the brain, intestinal tract, kidney, liver, and lung ( Liu and Pan, 2019). Transporter-mediated DDIs affect pharmacokinetics and pharmacodynamics, especially drug absorption and elimination ( Giacomini et al., 2010 Liu et al., 2015). Nowadays, more and more attention has been paid to the DDIs mediated by drug transporters. Drug transporters usually have extensive binding affinity toward a broad spectrum of small molecule substrates and inhibitors, suggesting their important role in DDIs ( Girardin, 2006 Koepsell, 2015 Liang et al., 2015). Movement of endogenous and exogenous chemicals across the biological membrane is usually mediated by transporter proteins that play a central role in the physiological function, pharmacological action, and elimination fate of these compounds. DDIs on one hand can enhance the efficacy of a drug and on the other hand may reduce the efficacy or even lead to toxic reactions to a drug ( Palleria et al., 2013 Sun et al., 2016 Niu et al., 2019). DDIs refer to the changes in toxicity, pharmacokinetics or pharmacodynamics of a drug when two or more drugs are applied simultaneously or sequentially ( Palleria et al., 2013 Prueksaritanont et al., 2013 Koepsell, 2015). Drug-drug interactions (DDIs) are among the critical factors in determining clinical drug disposition and response.
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