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, 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 microM, 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.
Hill
Erik R
ER
Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, United States of America.
Tian
Jinbin
J
Tilley
Michael R
MR
Zhu
Michael X
MX
Gu
Howard H
HH
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
D050486:Serotonin Plasma Membrane Transport Proteins; C076070:cocaine methiodide; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine