Kajiwara, Moto published the artcileRenal tubular secretion of varenicline by multidrug and toxin extrusion (MATE) transporters, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Drug Metabolism and Pharmacokinetics (2012), 27(6), 563-569, database is CAplus and MEDLINE.
Multidrug and toxin extrusion (MATE) 1 and MATE2-K, H+/organic cation antiporters, are located at the brush-border membrane of renal proximal tubules. The present study aimed to clarify the role of MATE transporters in tubular secretion of varenicline. Varenicline at a dose of 5 mg/kg was administered to wild-type and Mate1-knockout mice via the jugular vein, and its uptake was measured by high-performance liquid chromatog. The renal secretory clearance of and systemic exposure to varenicline were significantly decreased (54.6%, p < 0.05) and increased (116%, p < 0.05) resp., by the genetic disruption of Mate1 in mice. Uptake of varenicline and [14C]tetraethylammonium (TEA) was examined in HEK293 cells transiently expressing the human (h) MATE1, hMATE2-K, mouse (m) MATE1, and hOCT2 basolateral organic cation transporter. [14C]TEA uptake in HEK293 cells expressing MATE transporters and hOCT2 was decreased in the presence of varenicline. The calculated IC50 values for hMATE1, hMATE2-K, mMATE1, and hOCT2 were 62.2 ± 6.5, 122.3 ± 67.6, 255.0 ± 37.9, and 1,003.9 ± 135.8 (μM; mean ± S.E. for three sep. experiments), resp. Varenicline uptake was significantly increased in HEK293 cells expressing mMATE1, hMATE1, or hMATE2-K cDNA as well as hOCT2 compared to empty vector-transfected cells. In conclusion, renal MATE transporters were found to be responsible for renal tubular secretion of varenicline.
Drug Metabolism and Pharmacokinetics published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.
Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
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