The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function.

Article Details

Citation

Copy to clipboard

Zhu MY, Kyle PB, Hume AS, Ordway GA

The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function.

Neurochem Res. 2004 Feb;29(2):419-27.

PubMed ID

15002740 [ View in PubMed

]

Abstract

The present study examined the potential membrane retention of desipramine (DMI) following exposures of 293-hNET cells to DMI, and its effect on [3H]NE uptake. Incubation of cells with 500 nM DMI for 1 h or 1 day persistently inhibited the uptake of [3H]NE up to 7 days, despite daily repeated washing of cells with drug-free medium. Uptake inhibition was paralleled by persistent retention of DMI associated with cells, as determined by HPLC and by radiotracer experiments using [3H]DMI. [3H]DMI trapped in membranes was displaceable by the structurally unrelated NET inhibitor, nisoxetine, in a concentration-dependent manner, implying interaction of retained [3H]DMI with the NET. A similar cellular retention was observed following incubation of cells with nisoxetine. The results demonstrate that DMI and nisoxetine are persistently retained in cell membranes, at least partly in association with the NET. The retention and slow diffusion of DMI and nisoxetine from membranes may contribute to their pharmacological and modulatory action on NET.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Desipramine	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details