TABLE 9

Drugs that have been shown to inhibit human organic cation transporters and have not been tested for transport or could not be identified as substrate (only drugs for which an IC50 value <20 µM was determined for at least one OCT are indicated)

Charge of major microspecies at pH 7.4 was calculated with program MarvinSketch of ChemAxon. Abacavir: Minuesa et al., 2009, abemaciclib: Chappell et al., 2019, adapalene: Kido et al., 2011, alfuzosin: Chen et al., 2017a, amitriptyline: Sata et al., 2005; Ahlin et al., 2008; Zolk et al., 2009b; Belzer et al., 2013; Tzvetkov et al., 2013; Jouan et al., 2014; Hacker et al., 2015; Matthaei et al., 2016; Sandoval et al., 2018; Zhu et al., 2018, amadiaquine: van der Velden et al., 2017, D- amphetamine: Amphoux et al., 2006, amsacrine: Ahlin et al., 2008, artemisin: Hubeny et al., 2016, atomoxetine: Sandoval et al., 2018, azidothymidine: Minuesa et al., 2009, beclomethasone: Lips et al., 2005, benzethonium: Kido et al., 2011, benztropine: Sandoval et al., 2018, bithionol: Kido et al., 2011; Wittwer et al., 2013; Chen et al., 2017a, bosutinib: Johnston et al., 2014, bucindolol: Ahlin et al., 2008, 2011, budesonide: Lips et al., 2005, buflomedil: Kido et al., 2011; Hendrickx et al., 2013, buspirone: Wittwer et al., 2013, Sandoval et al., 2018, bisoprolol: Bachmakov et al., 2009, camylofine: Chen et al., 2017a, carbetapentane: Chen et al., 2017a, carvedilol: Bachmakov et al., 2009; Zolk et al., 2009b; Grube et al., 2011; Belzer et al., 2013; Yin et al., 2016; Chen et al., 2017a, clemastine: Ahlin et al., 2008, clomacran: Kido et al., 2011, chlorhexidine: Wittwer et al., 2013, cediranib: Johnston et al., 2014, chlorphenesin: Kido et al., 2011, chlorpromazine: Bednarczyk et al., 2003; Ahlin et al., 2008, 2011; Zolk et al., 2009a; Belzer et al., 2013, citalopram: Ahlin et al., 2008; Koepsell et al., unpublished data, clomipramine: Ahlin et al., 2008; Hendrickx et al., 2013, clonidine: Zhang et al., 1998; Wu et al., 2000; Müller et al., 2005; Suhre et al., 2005; Ahlin et al., 2008; Zolk et al., 2009a; Astorga et al., 2012; Belzer et al., 2013; Hendrickx et al., 2013; Tzvetkov et al., 2013; Chen et al., 2017a, closantel: Chen et al., 2017a, clotrimazole: Chen et al., 2017a, clozapine: Hendrickx et al., 2013; Wang et al., 2019, codeine: Tzvetkov et al., 2013, darunavir: Moss et al., 2015, dasatinib: Minematsu and Giacomini, 2011, des-fluoro(6)-quinolone: Okuda et al., 2006; Imamura et al., 2011; dextromethorphan: Chen et al., 2017a, dichlorophene: Chen et al., 2017a, desipramine: Gorboulev et al., 1997; Zhang et al., 1998; Wu et al., 2000; Ahlin et al., 2008, 2011; Tsuda et al., 2009b; Zolk et al., 2009b; Chen et al., 2017a, desloratadine: Zolk et al., 2009b, dicyclomine: Kido et al., 2011, dipyramidole: Kido et al., 2011, dobutamine: Chen et al., 2017a, dolutegravir: Reese et al., 2013; Lepist et al., 2014, domperidone: Wittwer et al., 2013, donepezil: Martínez-Guerrero et al., 2016; Matthaei et al., 2016, desloratadine: Zolk et al., 2009b, dihydroergotamine: Wittwer et al., 2013, doxazosin: Ahlin et al., 2011, doxepin: Zolk et al., 2009b; Belzer et al., 2013; Hacker et al., 2015; Chen et al., 2017a, eletriptan: Matthaei et al., 2016, epinastine: Wittwer et al., 2013, erlotinib: Minematsu and Giacomini, 2011; Chen et al., 2017a, esmolol: Martínez-Guerrero et al., 2016, ethinylestradiol: Wittwer et al., 2013, ethylacridinium: Belzer et al., 2013, exemestane: Kido et al., 2011, fenfluramine: Zolk et al., 2009a, flecainide: Umehara et al., 2008; Zolk et al., 2009b; Grube et al., 2011; Belzer et al., 2013, flurazepam: Zolk et al., 2009a,b, gabexate: Kido et al., 2011; Wittwer et al., 2013, gefitinib: Galetti et al., 2010; Minematsu and Giacomini, 2011, gentian violet: Kido et al., 2011, granisetron: Wittwer et al., 2013, griseofulvin: Chen et al., 2017a, guanabenz: Kido et al., 2011; Chen et al., 2017a, guanfacine: Astorga et al., 2012, imipramine: Wu et al., 2000; Ahlin et al., 2008; Tsuda et al., 2009b; Zolk et al., 2009b; Kido et al., 2011; Belzer et al., 2013; Hendrickx et al., 2013; Tzvetkov et al., 2013; Sandoval et al., 2018; Zhu et al., 2018, imiquimod: Astorga et al., 2012, indinavir: Zhang et al., 2000; Jung et al., 2008; Wittwer et al., 2013, irinotecan: Tzvetkov et al., 2013; Wittwer et al., 2013; Sandoval et al., 2018; Zhu et al., 2018, jatrorrhizine: Sun et al., 2019, ketoconazole: Ahlin et al., 2011; Astorga et al., 2012; Chen et al., 2017a, ketotifen: Martínez-Guerrero et al., 2016, lansoprazole: Nies et al., 2011a; Hacker et al., 2015, leukomycin: Wittwer et al., 2013, mebeverine: Kido et al., 2011, 3,4-methylenedioxymethamphetamine: Amphoux et al., 2006, mexiletine: Zolk et al., 2009b; Sandoval et al., 2018, mefloquine: Hubeny et al., 2016, midazolam: Zhang et al., 1998, mitoxantrone: Meyer zu Schwabedissen et al., 2010; Wittwer et al., 2013, nelfinavir: Zhang et al., 2000; Jung et al., 2008, nifekalant: Wittwer et al., 2013, nilotinib: Minematsu and Giacomini, 2011, ondansetron: Kido et al., 2011; Tzvetkov et al., 2012, 2013; Wittwer et al., 2013; Lechner et al., 2016; Zhu et al., 2018, oxaliplatin: Yonezawa et al., 2006; Yokoo et al., 2007, 2008; Ahlin et al., 2008, 2011; Jong et al., 2011; Sprowl et al., 2013, olanzapine: Kido et al., 2011, omeprazole: Nies et al., 2011a; Martínez-Guerrero et al., 2016, orphenadrine: Ahlin et al., 2008; Kido et al., 2011, pantoprazole: Nies et al., 2011a; Wittwer et al., 2013; Hacker et al., 2015, phenoxybenzamine: Hayer-Zillgen et al., 2002; Ahlin et al., 2008, phentoloamine: Astorga et al., 2012, phenyltoloxamine: Kido et al., 2011, phenytoin: Hasannejad et al., 2004, prochlorperazine: Ahlin et al., 2008; Hendrickx et al., 2013; Martínez-Guerrero et al., 2016, procyclidine: Kido et al., 2011, proguanil: Astorga et al., 2012; van der Velden et al., 2017, promazine: Ahlin et al., 2008, propafenone: Ahlin et al., 2008, 2011; Zolk et al., 2009b; Grube et al., 2011; Belzer et al., 2013; Hendrickx et al., 2013; Chen et al., 2017a, propantheline bromide: Kido et al., 2011, pyrimethamine: Matsushima et al., 2009; Tsuda et al., 2009b; Astorga et al., 2012; Hubeny et al., 2016; Lechner et al., 2016; Yin et al., 2016; Chen et al., 2017a; van der Velden et al., 2017, quetiapine: Wang et al., 2019, rabeprazole: Kido et al., 2011; Nies et al., 2011a, repaglinide: Ahlin et al., 2008; Bachmakov et al., 2008, rapamycin: Meyer zu Schwabedissen et al., 2010, rimantadine: Wittwer et al., 2013, ritonavir: Zhang et al., 2000; Jung et al., 2008; Meyer zu Schwabedissen et al., 2010; Wittwer et al., 2013; Lepist et al., 2014; Kikuchi et al., 2019, rosiglitazone: Bachmakov et al., 2008, saquinavir: Zhang et al., 2000; Jung et al., 2008, scopolamine: Hendrickx et al., 2013; Chen et al., 2017b, sitagliptin: Hacker et al., 2015, sparteine: Kido et al., 2011, spironolactone: Grube et al., 2006, 2011; Ahlin et al., 2011; Hacker et al., 2015, sulconazole: Kido et al., 2011, sunitinib: Minematsu and Giacomini, 2011; Chen et al., 2017a, tacrine: Kido et al., 2011; Astorga et al., 2012; Chen et al., 2017a; Sandoval et al., 2018; tenatoprazole: Nies et al., 2011a, tenofovir disoproxil: Minuesa et al., 2009; Shen et al., 2017, irtetrachlorosalicylanilide: Kido et al., 2011, tolterodine: Kido et al., 2011, tramadol: Astorga et al., 2012, trimipramine: Ahlin et al., 2008; Hacker et al., 2015, tripilenamine: Sandoval et al., 2018, tubocurarine: Wittwer et al., 2013, valspodar: Lechner et al., 2016, vecuronium: Wittwer et al., 2013, zafirlukast: Wittwer et al., 2013, ziprasidone: Wang et al., 2019, zolpidem: Hacker et al., 2015.

Drug (Charge of Major Microspecies at pH 7.4) Medical ApplicationIC50 [µM]
hOCT1hOCT2hOCT3hOCTN1hOCTN2hMATE1hMATE2-K
Abacavir (0) antiviral7 × 10−54 × 10−55 × 10−5
Abemaciclib (+) antineoplastic1.50.520.75
Adapalene (−) treatment of acne<1
Alfuzosin (+) antiprostate hyperplasia15
Amodiaquine (+) antimalarial11
Amsacrine (+) antineoplastic5
Amitriptyline (+) antidepressant1.9–580.4–14>100
Artemisin (0) antimalarial4.2
Atomoxetine (+) treatment of ADHS3.5–20
Atropine (+) mydriatic1.2, 121.3–294465.9a53a
Azidothymidine (+/−) antiviral0.00020.00030.0004
Beclomethasone (0) antiasthmatic4.4
Benzethonium (+) antineoplastic<1
Benztropine (+) anti-Parkinson0.3–13
Bithionol (−) anthelmintic2.21.9, <15.2a6.6a
Bucindolol (+) vasodilatory15, 27
Budesonide (0) antiasthmatic7.3
Buflomedil (+) vasodilatoryn.t.d.<1, n.t.d.
Buspirone (+) anxiolytic8.6–691.7a46a
Bisoprolol (+) antihypertensive2.4
Bosutinib (0) antichronic myeloic leukemia2.1
Camylofine (+) muscle relaxant9.1
Carbetapentane (+) antitussive1.6
Carvedilol (+) antihypertensive1.4, 3.42.3–637473124,a 146a79,a 131a
Cediranib (+) antineoplastic2.5
Chlorhexidine (++) antiseptic0.40.7a0.5a
Chlorphenesin (0) muscle relaxant<1
Chlorpromazine (+) antipsychotic2.6–522.6, 14
Clozapine (+) antidepressant1.8
Citalopram (+) antidepressant3, 1912145
Clemastine (+) antiallergic4.9
Clomacran (+) sedative and hypnotic<1
Clomipramine (+) antidepressant5, 19, n.t.d.n.t.d.
Clonidine (+) sedative0.6–23, n.t.d.2–63, n.t.d.110, 3738.1a54a
Cloperastine (+) antitussive15
Closantel (−) antiparasitc3
Clotrimazole (0) antifungal12
Clozapine (+) antipsychotic1.8, n.t.d.
Codeine (+) antitussive, analgesic11
Darunavir (0) antiviral16
Dasatinib (+) antineoplastic1.12.14.50.8a0.8a
Des-fluoro (6)-quinolone (c.n.d.) antibiotic0.9, 1.30.8a0.1a
Dextromethorphan (+) antitussive10
Dichlorophene (−) antifungal8.4
Dicyclomine (+) antispasmodic<1
Dipyramidole (0) antithrombotic812.62674
Donepezil (+) anti-Alzheimer0.8a–1.5a
Desipramine (+) antidepressant5–57161456a283a
Dihydroergotamine (+) antimigraine502.8a13a
Dobutamine (+) treatment of heart failure4.2
Dolutegravir (0) antiviral0.07, 1.9>1004.7a>100a
Domperidone (0) antemetic337.92.3a15a
Doxazosin (+) antihypertensive15
Doxepin (+) antidepressant1.5, 120.25–13
Eletriptan (0) antimigraine6.8
Epinastine (+) antiallergic<1, 4.31.1a30a
Erlotinib (0) antineoplastic0.34, 165.24.23.8,a 7.9a3.5,a 6.2a
Esmolol (+) treatment of tachycardia11a–25a
Ethinylestradiol (0) contraceptive2.221a20a
Ethylacridinium (+) antiseptic0.08
Exemestane (0) treatment of breast cancer<1
Fenfluramine (+) appetite suppressant10
Flecainide (+) antiarrhythmic2.5, 42191, 23460176
Flurazepam (+) anticonvulsant53, 60
Gabexate (+) anticoagulant0.90.5a–0.70a11a
Gefitinib (0) antineoplastic1.1245.51.8a0.19a
Gentian violet (+) fungicidal<1
Granisetron (+) antiemetic4.35.0a311a
Griseofulvin (0) antimycotic7.3
Guanabenz (+) antihypertensive4.9<1
Guanfacine (+) antihypertensive3.5a218a
Imipramine (+) antidepressant6–37, n.t.d.0.4–6, n.t.d.4242,a 10183a
Imiquimod (0) immune response modifier14a19a
Indinavir (0) antiviral37–208142, 275>5007.8a>500a
Irinotecan (+) antineoplastic1.4–210.31–16757.9a79a
Jatrorrhizine (+) promoting GI motility0.12, 0.820.18, 0.28
Ketoconazole (0) antifungal2.6, 7.41.3a9.3a
Ketotifen (+) antiallergic13a–27a
Lansoprazole (0) antacid363.3–9.53.1
Leukomycin (+−) antibiotic18211a125a
Mebeverine (+) antispasmodic<1
Mefloquine (+) antimalarial6.615
3,4-Methylenedioxymethamphetamine (+) stimulant241.674
Mexiletine (+) antiarrhythmic19–50
Midazolam (0) hypnotic, anesthetic3.7
Mitoxantrone (++) antineoplastic4473610.5a; 4.4; 5.20.83a
Nelfinavir (+) antiviral7, 2213
Nifekalant (++−) antiarrhythmic>30010.31466.5a2.7a
Nilotinib (0) antineoplastic2.9>300.353.4a1.8a
Ondansetron (+) antiemetic0.3–640.2–161.7, 170.04a–4.0a, 0.150.03a–1.7,a 6.9
Olanzapine (+) antipsychotic<1
Omeprazole (0) antacid166.72216–24a
Orphenadrine (+) muscle relaxant13, >1002.565>100
Pantoprazole (0) treatment of gastric ulcera31, >5000.56–2.823, 13743a>500a
Phenoxybenzamine (+) antihypertensive2.7, 1556
Phentolamine (+) vasodilatory4.6a5.3a
Phenyltoloxamine (+) enhancer of analgetics<1
Phenytoin (0) anticonvulsant0.75
Prochlorperazine (+) antipsychotic50, n.t.d.n.t.d.7.9a–15a
Procyclidine (+) anti-Parkinson<0.1
Proguanil (+) antimalarial134.4a1.4a
Promazine (+) antipsychotic17
Propafenone (+) antiarrhythmic1–16, n.t.d.3.6, 25, n.t.d.68
Propantheline (+) treatment of hyperhidrosis<1
Pyrimethamine (+) antimalarial8.5, 141.6–230.04a–1.2a, 0.080.01a–0.83,a 0.06
Quetiapine (0) antidepressant13
Rabeprazole (0) antacid3.0<1, 5.73.0
Repaglinide (0) antidiabetic1.6, 9.2
Rapamycin (0) immune suppressive3.3, 3.5
Rimantadine (+) antiviral4.47.3a288a
Ritonavir (0) antiviral5–3420, 25>1001.3a–4.4a 14, 1524,a 90a
Rosiglitazone (−) antidiabetic6.9
Saquinavir (+) antiviral8, 37205
Scopolamine (0) antiemetic6.7, n.t.d.541, n.t.d.218119a700a
Sitagliptin (+) antidiabetic7.4
Sparteine (++) anticonvulsant, antiarrhythmic<1
Spironolactone (0) antihypertensive1.2, 31.37312526, 36
Sulconazole (0) antifungal<1
Sunitinib (+) antineoplastic0.33, 6.11.75.20.28a0.86
Tacrine (+) anti-Alzheimer22, 830.4–2.30.5a, 1.11.1,a >100
Tenatoprazole (0) antacid232015
Tenofovir disopoxil (0) antiviral9 × 10−5, >106 × 10−55 × 10−7
Tetrachlorosalicylanilide (−) antiseptic<1
Tolterodine (+) spasmolyticum<1
Tramadol (+)18a75a
Trimipramine (+) antidepressant280.44
Tripelenamine (+) antiallergic2.1–12
Tubocurarine (++) muscle relaxant799.4a56a
Valspodar (0), antidrug resistant2.0a–>15a0.11a–0.24a
Vecuronium (++) muscle relaxant3.51.9a25a
Zafirlukast (−) antiasthmatic9.74.3a7.6a
Ziprasidone (0) antidepressant3.6
Zolpidem (0) sedative, anticonvulsant0.15
  • c.n.d., charge not determined; GI, gastrointestinal; n.t.d., no transport detected under the employed experimental conditions.

  • a Uptake measurements performed in presence of an outwardly directed proton gradient.