Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers.
J Neural Transm (Vienna)
; 109(10): 1229-40, 2002 Oct.
Article
en En
| MEDLINE
| ID: mdl-12373557
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
/
Neuropéptidos
/
Monoaminas Biogénicas
/
Proteínas Portadoras
/
Efedrina
Límite:
Animals
Idioma:
En
Revista:
J Neural Transm (Vienna)
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos