Comparison of the kinetic characteristics of inhibitory effects exerted by biguanides and H2-blockers on human and rat organic cation transporter-mediated transport: Insight into the development of drug candidates

Xenobiotica. 2007 Jun;37(6):618-34. doi: 10.1080/00498250701397705.


In this study, the comparison of the transport of substrates (1-methyl-4-phenylpydinium (MPP) and tetraethyl ammonium (TEA)) and the inhibition potency of the inhibitors (biguanides and H(2)-blockers) for human and rat organic cation transporters (hOCTs and rOcts), and the inhibition type of inhibitors for these transporters were investigated using HEK293 cells that stably express hOCT/rOct. The concentration-dependent uptake of [(3)H]-MPP and [(14)C]-TEA by hOCT1-3/rOct1-3 had K(m) values similar to those in the literature. It was also deduced that MPP and TEA are competitive inhibitors for hOCT1-2/rOct1-2. The K(i) values for phenformin inhibition of [(3)H]-MPP and [(14)C]-TEA uptake by hOCT1-3/rOct1-3 were lower than that for metformin. The [(3)H]-MPP uptake by hOCT1/rOct1 and hOCT3/rOct3 was inhibited by famotidine and ranitidine whereas that by hOCT2/rOct2 was not. The inhibitory potency of cimetidine for hOCT1-2 was very weak. In most cases, the differences in the V(max)/K(m) values of substrates and the K(i) values of inhibitors between hOCT and rOct were minor. The acquisition of information on OCT/Oct mediated-transport and/or inhibition such as that presented in this report is very useful for further understanding of certain aspects of uptake, distribution, and excretion for drug candidates.

Publication types

  • Comparative Study

MeSH terms

  • 1-Methyl-4-phenylpyridinium / metabolism
  • Animals
  • Biguanides / pharmacology*
  • Cell Line
  • Cimetidine / pharmacology
  • Drug Design
  • Famotidine / pharmacology
  • Histamine H2 Antagonists / pharmacology*
  • Humans
  • Ion Transport / drug effects
  • Kinetics
  • Metformin / pharmacology
  • Organic Cation Transport Proteins / antagonists & inhibitors*
  • Phenformin / pharmacology
  • Ranitidine / pharmacology
  • Rats
  • Tetraethylammonium / metabolism


  • Biguanides
  • Histamine H2 Antagonists
  • Organic Cation Transport Proteins
  • Famotidine
  • Tetraethylammonium
  • Cimetidine
  • Ranitidine
  • Metformin
  • Phenformin
  • 1-Methyl-4-phenylpyridinium