Pharmacological role of efflux transporters: Clinical implications for medication use during breastfeeding

Ahmadzai, Hilai; Tee, Lisa; Crowe, Andrew

doi:10.5497/wjp.v3.i4.153

Cited by 4 publications

(3 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(B) Blood-intestine barrier [10,20,201,[225][226][227][228]. (C) Blood-milk barrier in mammary glands [229][230][231]. (D) Blood-bile barrier in the liver [20,201,225,[232][233][234][235][236].…”

Section: Introduction-evolution and Function Of The Small Molecule Trmentioning

confidence: 99%

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Nicklisch

Hamdoun

2020

FEBS Letters

View full text Add to dashboard Cite

Small molecule transporters (SMTs) in the ABC and SLC families are important players in disposition of diverse endo-and xenobiotics. Interactions of environmental chemicals with these transporters were first postulated in the 1990s, and since validated in numerous in vitro and in vivo scenarios. Recent results on the co-crystal structure of ABCB1 with the flame-retardant BDE-100 demonstrate that a diverse range of man-made and natural toxic molecules, hereafter termed transporter-interfering chemicals (TICs), can directly bind to SMTs and interfere with their function. TIC-binding modes mimic those of substrates, inhibitors, modulators, inducers, and possibly stimulants through direct and allosteric mechanisms. Similarly, the effects could directly or indirectly agonize, antagonize or perhaps even prime the SMT system to alter transport function. Importantly, TICs are distinguished from drugs and pharmaceuticals that interact with transporters in that exposure is unintended and inherently variant. Here, we review the molecular mechanisms of environmental chemical interaction with SMTs, the methodological considerations for their evaluation, and the future directions for TIC discovery.

show abstract

Section: Introduction-evolution and Function Of The Small Molecule Trmentioning

confidence: 99%

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Nicklisch

Hamdoun

2020

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Transport proteins of the ABC family for the efflux of APs across the BBB are increasingly recognized as important determinants of the distribution of APs in the CNS and their excretion from the brain [27,41]. The P-gp as transport protein in many cases has shown itself to be a key element of the BBB, which can actively transport a huge number of lipophilic drugs from the endothelial cells of the brain capillaries that form the BBB.…”

Section: Efflux Transportmentioning

confidence: 99%

“…The implications of all these transport proteins at BBB level include the minimization or prevention of AP-induced neurotoxic ADRs [13,35,36,41] and aggravating SSDs [11,36] or development of pseudoresistance to APs [11,13]. On the other hand, ABC transport proteins may also limit the central distribution of APs used to treat SSDs, increasing the risk of developing therapeutic resistance [13,36,39].…”

Section: Efflux Transportmentioning

confidence: 99%

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins

Насырова

Shnayder

Osipova

et al. 2023

Genes

View full text Add to dashboard Cite

Antipsychotic (AP)—induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel “Transporter protein (PT)—Antipsychotic (AP) Pharmacogenetic test (PGx)” (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.

show abstract

Direct oral anticoagulant safety during breastfeeding: a narrative review

Daei

Khalili

Heidari

2021

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Pharmacological role of efflux transporters: Clinical implications for medication use during breastfeeding

Cited by 4 publications

References 77 publications

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins

Direct oral anticoagulant safety during breastfeeding: a narrative review

Contact Info

Product

Resources

About