Drug-Drug Interactions at Organic Cation Transporter 1

Zhou, Shiwei; Zeng, Su; Shu, Yan

doi:10.3389/fphar.2021.628705

Cited by 22 publications

(18 citation statements)

References 165 publications

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“…Genetic factors may contribute to the vulnerability to and impacts of DDI in patients with one or multiple diseases, largely through the regulation of the DDI biological responses. Genetic polymorphisms have been demonstrated in genes coding for drug metabolizing processes, including cytochrome P450 ( Turner et al., 2020 ), or transporting proteins, such as p-glycoprotein ( Holtzman et al., 2006 ) and organic cation transporter (OCT) ( Zhou et al., 2021 ).…”

Section: Polypharmacology Pharmacogenomics and Pharmacointeractomesmentioning

confidence: 99%

Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions

Geng

Madonna

Hermida

et al. 2021

Current Research in Pharmacology and Drug Discovery

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This article summarizes the current literature and documents new evidence concerning drug-drug interactions (DDI) stemming from pharmacogenomic and circadian rhythm determinants of therapies used to treat common cardiovascular diseases (CVD), such as atherosclerosis and hypertension. Patients with CVD often have more than one pathophysiologic condition, namely metabolic syndromes, hypertension, hyperlipidemia, and hyperglycemia, among others, which necessitate polytherapeutic or polypharmaceutic management. Interactions between drugs, drugs and food/food supplements, or drugs and genetic/epigenetic factors may have adverse impacts on the cardiovascular and other systems of the body. The mechanisms underlying cardiovascular DDI may involve the formation of a complex pharmacointeractome, including the absorption, distribution, metabolism, and elimination of drugs, which affect their respective bioavailability, efficacy, and/or harmful metabolites. The pharmacointeractome of cardiovascular drugs is likely operated with endogenous rhythms controlled by circadian clock genes. Basic and clinical investigations have improved the knowledge and understanding of cardiovascular pharmacogenomics and pharmacointeractomes, and additionally they have presented new evidence that the staging of deterministic circadian rhythms, according to the dosing time of drugs, e.g., upon awakening vs. at bedtime, cannot only differentially impact their pharmacokinetics and pharmacodynamics but also mediate agonistic/synergetic or antagonistic DDI. To properly manage CVD patients and avoid DDI, it is important that clinicians have sufficient knowledge of their multiple risk factors, i.e., age, gender, and life style elements (like diet, smoking, psychological stress, and alcohol consumption), and comorbidities, such as diabetes, hypertension, dyslipidemia, and depression, and the potential interactions between genetic or epigenetic background of their prescribed therapeutics.

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Section: Polypharmacology Pharmacogenomics and Pharmacointeractomesmentioning

confidence: 99%

Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions

Geng

Madonna

Hermida

et al. 2021

Current Research in Pharmacology and Drug Discovery

View full text Add to dashboard Cite

show abstract

“…The isoform 1 (OCT1) is majorly accountable for drug accumulation in the liver. 32 Drug compounds which are organic cation transporter substrates in tissues, can cause drug toxicity in certain organs. The prediction results indicate that the test compounds and cyclophosphamide are not substrates for organic cation transporters (OCT), so they do not cause organ toxicity.…”

Section: Resultsmentioning

confidence: 99%

In Silico Evaluation of the Physicochemical, Pharmacokinetics, and Toxicity Profiles of Sesquiterpene Lactones of South African Leaf (Vernonia amygdalina Delile)

2021

TJNPR

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“…However, a growing number of studies shows that the low-affinity, high-capacity organic cation transporters (OCT1–3), as well as the plasma membrane monoamine transporter (PMAT), are also distinctly involved in monoamine reuptake from the synaptic cleft [ 11 , 25 ]. Furthermore, they transport and eliminate xenobiotics in the periphery, lending them pharmacological and clinical relevance [ 11 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction Profiles of Central Nervous System Active Drugs at Human Organic Cation Transporters 1–3 and Human Plasma Membrane Monoamine Transporter

Angenoorth

Stankovic

Niello

et al. 2021

IJMS

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Many psychoactive compounds have been shown to primarily interact with high-affinity and low-capacity solute carrier 6 (SLC6) monoamine transporters for norepinephrine (NET; norepinephrine transporter), dopamine (DAT; dopamine transporter) and serotonin (SERT; serotonin transporter). Previous studies indicate an overlap between the inhibitory capacities of substances at SLC6 and SLC22 human organic cation transporters (SLC22A1–3; hOCT1–3) and the human plasma membrane monoamine transporter (SLC29A4; hPMAT), which can be classified as high-capacity, low-affinity monoamine transporters. However, interactions between central nervous system active substances, the OCTs, and the functionally-related PMAT have largely been understudied. Herein, we report data from 17 psychoactive substances interacting with the SLC6 monoamine transporters, concerning their potential to interact with the human OCT isoforms and hPMAT by utilizing radiotracer-based in vitro uptake inhibition assays at stably expressing human embryonic kidney 293 cells (HEK293) cells. Many compounds inhibit substrate uptake by hOCT1 and hOCT2 in the low micromolar range, whereas only a few substances interact with hOCT3 and hPMAT. Interestingly, methylphenidate and ketamine selectively interact with hOCT1 or hOCT2, respectively. Additionally, 3,4-methylenedioxymethamphetamine (MDMA) is a potent inhibitor of hOCT1 and 2 and hPMAT. Enantiospecific differences of R- and S-α-pyrrolidinovalerophenone (R- and S-α-PVP) and R- and S-citalopram and the effects of aromatic substituents are explored. Our results highlight the significance of investigating drug interactions with hOCTs and hPMAT, due to their role in regulating monoamine concentrations and xenobiotic clearance.

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Drug-Drug Interactions at Organic Cation Transporter 1

Cited by 22 publications

References 165 publications

Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions

Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions

In Silico Evaluation of the Physicochemical, Pharmacokinetics, and Toxicity Profiles of Sesquiterpene Lactones of South African Leaf (Vernonia amygdalina Delile)

Interaction Profiles of Central Nervous System Active Drugs at Human Organic Cation Transporters 1–3 and Human Plasma Membrane Monoamine Transporter

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