Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers.

Article Details

Citation

Foley KF, Van Dort ME, Sievert MK, Ruoho AE, Cozzi NV

Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers.

J Neural Transm (Vienna). 2002 Oct;109(10):1229-40.

PubMed ID
12373557 [ View in PubMed
]
Abstract

Meta-hydroxyephedrine (HED) comprises four stereoisomers consisting of two enantiomeric pairs related to ephedrine and pseudoephedrine. HED is transported into adrenergic neurons and radiolabeled HED has been employed in positron emission tomography (PET) to image adrenergic neurons in vivo. To extend structure-activity analyses of binding sites within monoamine transporters and to determine which stereoisomer displayed the best selectivity for PET imaging applications, we tested the HED compounds for their abilities to inhibit [(3)H]neurotransmitter uptake into platelets, transfected cells, and chromaffin vesicles. We hypothesized that the HED compounds would be most potent at the norepinephrine transporter (NET) compared to the serotonin or dopamine transporters and that the 1R diastereomers would be more effective than 1S diastereomers. Supporting the hypotheses, all stereoisomers were most potent at the NET and the 1R,2S stereoisomer was the most potent inhibitor overall. However, the 1S,2R isomer may be preferred for PET applications because of better selectivity among the transporters and reduced neuronal recycling.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
PseudoephedrineSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
PseudoephedrineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
PseudoephedrineSodium-dependent dopamine transporterProteinHumans
Unknown
Inhibitor
Details
PseudoephedrineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
PseudoephedrineSodium-dependent serotonin transporterProteinHumans
Unknown
Inhibitor
Details