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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 27, Number 3, April 2003,
pp. 125-134
Cocaine, Benzoylecgonine, Amphetamine, and N-Acetylamphetamine
Binding to Melanin Subtypes*
Chad R. Borges[1], Jeanette C. Roberts[2], Diana
G. Wilkins[1], and
Douglas E. Rollins[1]
[1]Department of Pharmacology and Toxicology
[2]Department of Medicinal Chemistry,
University of Utah, Salt Lake City, Utah
Experiments have been performed to document
the in vitro binding of cocaine, benzoylecgonine (BE), amphetamine, and N-acetylamphetamine
(N-AcAp) to synthetic melanin subtypes. The two predominant melanin types
in hair are the black eumelanins and the reddish-brown pheomelanins. The
melanins included in this study are two black eumelanin subtypes [5,6-dihydroxyindole
(DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) derived melanins],
a reddish-brown pheomelanin [from 5-cysteinyl-S-Dopa (5-CysDOPA)], and two
mixed eu-/pheomelanin copolymers. Results indicate that the basic drugs cocaine
and amphetamine bind to eumelanins and mixed eu-/pheomelanins to varying
degrees, but not to pure pheomelanin. BE and N-AcAp, net neutral molecules,
do not bind to any type of melanin. As a model of which eumelanin chemical
functional groups bind drugs, amphetamine was shown, using tandem mass spectrometry,
to form a noncovalent adduct with dimerized oxidized catechol. Similar functional
groups on the eumelanin polymer may represent an important drug-binding site.
Overall, these findings show that basic drugs have a greater affinity for
melanin than their net neutral analogues, reveal that melanin types differ
when it comes to drug binding, help elucidate what properties of melanin
are important for drug binding, and help explain why hair color biases exist. Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
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