WIN 35,428 and mazindol are mutually exclusive in binding to the cloned human dopamine transporter.

Abstract	It has been suggested that cocaine and mazindol bind to separate sites on the dopamine transporter. In the present study, we address this issue by examining the inhibition by mazindol of the binding of [3H]WIN 35,428 ([3H]2beta-carbomethyoxy-3beta-(4-fluorophenyl)-tropane), a phenyltropane analog of cocaine, and the inhibition by WIN 35,428 of [3H]mazindol binding to the cloned human dopamine transporter expressed in C6 glioma cells. The design involved the construction of inhibition curves at six widely different radioligand levels, enabling the distinction between the nonlinear hyperbolic competition (i.e., negative allosteric) model and the competitive (i.e., mutually exclusive binding) model. Nonlinear computer curve-fitting analysis indicated no difference in the goodness of fit between the two models; the negative allosteric model indicated an extremely high allosteric constant of approximately > or = 100, which practically equates to the competitive model. The present results suggest that complex interactions reported between cocaine and mazindol in inhibiting dopamine transport are beyond the level of ligand recognition.
Authors	C Xu, M E Reith
Journal	The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 282 Issue 2 Pg. 920-7 (Aug 1997) ISSN: 0022-3565 [Print] United States
PMID	9262359 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Carrier Proteins Dopamine Plasma Membrane Transport Proteins Dopamine Uptake Inhibitors Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins Recombinant Proteins Tritium (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester Mazindol Cocaine Dopamine
Topics	Binding, Competitive Carrier Proteins (genetics, metabolism) Cloning, Molecular Cocaine (analogs & derivatives, metabolism) Dopamine (metabolism) Dopamine Plasma Membrane Transport Proteins Dopamine Uptake Inhibitors (metabolism) Humans Mazindol (metabolism) Membrane Glycoproteins Membrane Transport Proteins Models, Chemical Nerve Tissue Proteins Radioligand Assay Recombinant Proteins (genetics, metabolism) Tritium Tumor Cells, Cultured

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