2′-Substitution of cocaine selectively enhances dopamine and norepinephrine transporter binding
| Autor: | Kwasi S. Avor, Nicolas Hall, Garo P. Basmadjian, Satendra Singh, Hui-Min Chan, Thomas W. Seale |
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| Rok vydání: | 1997 |
| Předmět: |
Dopamine
Nerve Tissue Proteins Motor Activity Pharmacology Binding Competitive Rats Sprague-Dawley Norepinephrine Cocaine Fluoxetine medicine Animals Dopamine transporter Cocaine binding Dopamine Plasma Membrane Transport Proteins Membrane Glycoproteins Norepinephrine Plasma Membrane Transport Proteins Symporters biology Chemistry General Neuroscience Brain Membrane Transport Proteins Transporter Nisoxetine Rats Paroxetine Norepinephrine transporter biology.protein Catecholamine Carrier Proteins medicine.drug |
| Zdroj: | NeuroReport. 8:3571-3575 |
| ISSN: | 0959-4965 |
| DOI: | 10.1097/00001756-199711100-00030 |
| Popis: | Few studies have characterized the effect of substituents at the 2'-position of cocaine on transporter binding potency and selectivity. We synthesized 2'-OH-, 2'-F- and 2'-acetoxy-cocaines and compared their binding potencies for rat dopamine, norepinephrine and 5-hydroxytryptamine transporters to cocaine, 3'-OH-, 4'-OH-, 2'-OH,4'-I-cocaine derivatives, and to the transporter selective ligands WIN 35,428, nisoxetine and paroxetine. Unlike most substitutions, 2'-OH- and 2'-acetoxy-groups increased cocaine's binding potency for the dopamine transporter (10- and 4-fold, respectively). These substituents also enhanced binding to the norepinephrine transporter (52- and 35-fold, respectively) but had less effect on 5-hydroxytryptamine transporter binding. 2'-Hydroxylation also enhanced binding of 4'-I cocaine, an analog with low DA binding potency. The ability of 2'-substituents to substantially increase cocaine binding potency and to alter selectivity for brain transporters indicates the potential importance of the 2'-position in transporter binding. |
| Databáze: | OpenAIRE |
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