Molecular Pharmacology, Vol 14, 856-867, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Methadone Uptake by L5178Y Mouse Leukemic Cells

¹ Department of Biochemistry, University of Missouri, Columbia, Missouri 65201

Mouse leukemic cells accumulate methadone at 37° while at 0° drug associated with the cells is constant. After a suitable incubation period the accumulation at 37° ceases and the net drug associated with the cells remains constant. This steady-state level (37° uptake minus 0° uptake) increases in proportion to the free drug concentration up to at least 0.7 mM methadone where the cells contain 2.5 fmol/cell. The cells apparently concentrate methadone at 7.5-16 times the medium concentration. The rate of uptake appears to be a complex function of the free methadone concentration in the medium, however, no definite saturation was observed. The loss of [³H]methadone from cells preloaded with drug is very rapid and the extent of loss is independent of the concentration of methadone in the medium. Methadone appears to be only weakly bound by the cells and is readily accessible to the medium. Various metabolic inhibitors do not reduce methadone uptake; further, the results of competition experiments with other opiates and the stereoisomers of methadone reveal little, if any, uptake specificity for methadone. We conclude that methadone is accumulated by passive diffusion which may involve extensive intracellular binding of the drug by macromolecules and/or partitioning of the drug into hydrophobic regions of the cell.