PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS
This article describes basic information about the classification, structure, substrate specificity and expression of organic cation transporters. The pharmacokinetic and pharmacogenetic aspects of transporters are discussed in more detail, as well as their participation in drug-drug interactions. O...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | Russian |
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Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»
2018-06-01
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| Series: | Безопасность и риск фармакотерапии |
| Subjects: | |
| Online Access: | https://www.risksafety.ru/jour/article/view/104 |
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| author | V. A. Evteev R. E. Kazakov O. A. Muslimova E. Yu. Demchenkova |
| author_facet | V. A. Evteev R. E. Kazakov O. A. Muslimova E. Yu. Demchenkova |
| author_sort | V. A. Evteev |
| collection | DOAJ |
| description | This article describes basic information about the classification, structure, substrate specificity and expression of organic cation transporters. The pharmacokinetic and pharmacogenetic aspects of transporters are discussed in more detail, as well as their participation in drug-drug interactions. Organic cation transporters are members of the SLC family which include three isoforms: OCT1, OCT2, OCT3. They are similar in structure to other members of this family and have 12 transmembrane domains. OCT1 is expressed predominantly in the liver, OCT2 in the kidneys, and OCT3 is the most common among all transports of this family and is expressed in the liver, placenta, kidneys, skeletal muscles, heart and brain. The regulation of transporter expression is mainly due to the presence of glycosylation and phosphorylation sites in large loops between 1,2 and 6,7 transmembrane domains, respectively. Among the endogenous substrates OCT — catecholamines, neurotransmitters, steroid hormones, etc. Among drugs, substrates of OCT are: metformin, ganciclovir, procainamide, cisplatin, cimetidine, etc. All three OCT genes are located in one cluster with a length of 300,000 bp. on the long arm of the 6th chromosome. For OCT1 the four most studied polymorphisms are known: rs12208357, rs34130495, rs72552763 and rs34059508. For OCT2, the only clinically relevant polymorphism is rs316019. For OCT3 at the moment, there are 4 polymorphisms: A116S, T400I, A439V, and M370I. Drug-drug interactions involving OCT occur when the substrate is inhibitor of the transporter. The effect of cimetidine and platinum drugs on the pharmacokinetics of drugs has been most studied. Organic cation transporters are currently being actively studied. Every year the number of drugs that are substrates of OCT is growing. |
| first_indexed | 2024-03-08T22:27:07Z |
| format | Article |
| id | doaj.art-25b536591303417dace1019884dbc22c |
| institution | Directory Open Access Journal |
| issn | 2312-7821 2619-1164 |
| language | Russian |
| last_indexed | 2025-03-14T10:50:45Z |
| publishDate | 2018-06-01 |
| publisher | Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» |
| record_format | Article |
| series | Безопасность и риск фармакотерапии |
| spelling | doaj.art-25b536591303417dace1019884dbc22c2025-03-02T10:50:03ZrusMinistry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»Безопасность и риск фармакотерапии2312-78212619-11642018-06-0162788510.30895/2312-7821-2018-6-2-78-85104PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERSV. A. Evteev0R. E. Kazakov1O. A. Muslimova2E. Yu. Demchenkova3Scientific Centre for Expert Evaluation of Medicinal ProductsScientific Centre for Expert Evaluation of Medicinal ProductsScientific Centre for Expert Evaluation of Medicinal ProductsScientific Centre for Expert Evaluation of Medicinal ProductsThis article describes basic information about the classification, structure, substrate specificity and expression of organic cation transporters. The pharmacokinetic and pharmacogenetic aspects of transporters are discussed in more detail, as well as their participation in drug-drug interactions. Organic cation transporters are members of the SLC family which include three isoforms: OCT1, OCT2, OCT3. They are similar in structure to other members of this family and have 12 transmembrane domains. OCT1 is expressed predominantly in the liver, OCT2 in the kidneys, and OCT3 is the most common among all transports of this family and is expressed in the liver, placenta, kidneys, skeletal muscles, heart and brain. The regulation of transporter expression is mainly due to the presence of glycosylation and phosphorylation sites in large loops between 1,2 and 6,7 transmembrane domains, respectively. Among the endogenous substrates OCT — catecholamines, neurotransmitters, steroid hormones, etc. Among drugs, substrates of OCT are: metformin, ganciclovir, procainamide, cisplatin, cimetidine, etc. All three OCT genes are located in one cluster with a length of 300,000 bp. on the long arm of the 6th chromosome. For OCT1 the four most studied polymorphisms are known: rs12208357, rs34130495, rs72552763 and rs34059508. For OCT2, the only clinically relevant polymorphism is rs316019. For OCT3 at the moment, there are 4 polymorphisms: A116S, T400I, A439V, and M370I. Drug-drug interactions involving OCT occur when the substrate is inhibitor of the transporter. The effect of cimetidine and platinum drugs on the pharmacokinetics of drugs has been most studied. Organic cation transporters are currently being actively studied. Every year the number of drugs that are substrates of OCT is growing.https://www.risksafety.ru/jour/article/view/104transportersorganic cationspharmacogeneticssnpslcslc22aoct1oct2oct3 |
| spellingShingle | V. A. Evteev R. E. Kazakov O. A. Muslimova E. Yu. Demchenkova PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS Безопасность и риск фармакотерапии transporters organic cations pharmacogenetics snp slc slc22a oct1 oct2 oct3 |
| title | PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS |
| title_full | PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS |
| title_fullStr | PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS |
| title_full_unstemmed | PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS |
| title_short | PHARMACOGENETICS OF ORGANIC CATION TRANSPORTERS |
| title_sort | pharmacogenetics of organic cation transporters |
| topic | transporters organic cations pharmacogenetics snp slc slc22a oct1 oct2 oct3 |
| url | https://www.risksafety.ru/jour/article/view/104 |
| work_keys_str_mv | AT vaevteev pharmacogeneticsoforganiccationtransporters AT rekazakov pharmacogeneticsoforganiccationtransporters AT oamuslimova pharmacogeneticsoforganiccationtransporters AT eyudemchenkova pharmacogeneticsoforganiccationtransporters |