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Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice

Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC(50) values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinep...

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Detalles Bibliográficos
Autores principales: Hill, Erik R., Tian, Jinbin, Tilley, Michael R., Zhu, Michael X., Gu, Howard H.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762027/
https://www.ncbi.nlm.nih.gov/pubmed/19855831
http://dx.doi.org/10.1371/journal.pone.0007578
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author Hill, Erik R.
Tian, Jinbin
Tilley, Michael R.
Zhu, Michael X.
Gu, Howard H.
author_facet Hill, Erik R.
Tian, Jinbin
Tilley, Michael R.
Zhu, Michael X.
Gu, Howard H.
author_sort Hill, Erik R.
collection PubMed
description Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC(50) values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinephrine, and serotonin transporters, and sodium channels. Using cells transfected with individual transporters from mice and synaptosomes from mouse striatum tissues, we observed that the inhibition IC(50) values for monoamine uptake by CM were 31-fold to 184-fold higher compared to cocaine at each of the transporters. In dorsal root ganglion neurons, cocaine inhibited sodium channels with an apparent IC(50) of 75 µM, while CM showed no observable effect at concentrations up to 3 mM. These results indicate that an equal dose of CM will not produce an equivalent peripheral effect of cocaine.
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spelling pubmed-27620272009-10-26 Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice Hill, Erik R. Tian, Jinbin Tilley, Michael R. Zhu, Michael X. Gu, Howard H. PLoS One Research Article Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC(50) values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinephrine, and serotonin transporters, and sodium channels. Using cells transfected with individual transporters from mice and synaptosomes from mouse striatum tissues, we observed that the inhibition IC(50) values for monoamine uptake by CM were 31-fold to 184-fold higher compared to cocaine at each of the transporters. In dorsal root ganglion neurons, cocaine inhibited sodium channels with an apparent IC(50) of 75 µM, while CM showed no observable effect at concentrations up to 3 mM. These results indicate that an equal dose of CM will not produce an equivalent peripheral effect of cocaine. Public Library of Science 2009-10-26 /pmc/articles/PMC2762027/ /pubmed/19855831 http://dx.doi.org/10.1371/journal.pone.0007578 Text en Hill et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hill, Erik R.
Tian, Jinbin
Tilley, Michael R.
Zhu, Michael X.
Gu, Howard H.
Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
title Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
title_full Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
title_fullStr Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
title_full_unstemmed Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
title_short Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice
title_sort potencies of cocaine methiodide on major cocaine targets in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762027/
https://www.ncbi.nlm.nih.gov/pubmed/19855831
http://dx.doi.org/10.1371/journal.pone.0007578
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