Читать книгу Drug Transporters - Группа авторов - Страница 34

Compounds that are commonly transported by hOCT1 include the model cations MPP⁺, TEA, tetrapropylammonium (TPrA), tetrabutylammonium (TBuA), N‐methylquinine, and N‐(4.4‐azo‐n‐pentyl)‐21‐deoxyajmalinium, the endogenous compounds choline, acetylcholine and agmatine, and the drugs quinidine, quinine, acyclovir, ganciclovir, metformin, sumatriptan, ondansetron, morphine, and several anticancer agents, e.g., anthracyclines (Table 2.2) [16]. Both human and mouse OCT1 are high‐capacity thiamine (vitamin B1) transporters that respond to the uptake of dietary thiamine to liver [18]. The series of n‐tetraalkylammonium (nTAA) compounds has been shown to have different affinity among human, rabbit, rat, and mouse OCT1. While the larger nTAAs are transported at greater rate in hOCT, the smaller nTAAs are transported at greater rate in rOCT1 or mOCT1 [19]. It is suggested that molecular mass or hydrophobicity may affect differences in recognition of OCT substrates across species. In terms of inhibition, some inhibitors of OCTs show differences in potency among the individual subtypes. For example, the inhibition potency of phencyclidine, diphenhydramine, prazosin, citalopram, and atropine is greater for hOCT1 compared with hOCT2 and hOCT3. In contrast, corticosterone shows stronger inhibition on hOCT3 than OCT1 [1]. Besides influx transport, OCT1 has been demonstrated as an efflux transporter of acylcarnitine from liver to plasma [20].