3H-Nicotine, 3H-Flunitrazepam, and 3H-Cocaine Incorporation Into Melanin: A Model for the Examination of Drug-Melanin Interactions

Abstract

To explore drug-melanin interactions, we examined the in vitro tyrosinase-mediated formation of melanin from tyrosine in the presence of the 3H-cocaine (3H-COC), 3H-flunitrazepam (3H-FLU), and 3H-nicotine (3H-NIC) at 10-100,000 ng/mL. Polymerization in the presence of 10 or 100 ng/mL of each drug resulted in almost complete drug incorporation into the melanin pellet. Only 12% (3H-NIC) to 28% (3H-FLU) of the pellet-associated radioactivity could be released upon treatment with 6 M HCl. At 1000-100,000 ng/mL, between 20 and 50% of label became melanin-associated. In each case a significant percentage of melanin-associated radioactivity was resistant to treatment with 6 M HCl. Nicotine-associated radioactivity in the polymer was subject to much greater quenching than was 3H-COC or 3H-FLU, suggesting a much tighter association with the melanin. The subsequent demonstration of a covalent adduct of a melanin intermediate and nicotine has demonstrated the utility of this polymerization system as a model for further chemical characterization of drug-melanin interactions.

Association of Melanin Pigmentation in the Gingiva of Children With Parents Who Smoke

“…An already high prevalence of gingival pigmentation was enhanced excessively by active smoking. 4 The stimulatory effect could be explained by high-affinity activity of polycyclic amines such as nicotine 24 and benzpyrene 25 in tobacco smoke on melanin; noxious substances in the epithelial cells were eliminated.…”

Nicotine in the hair of mummies from San Pedro de Atacama (Northern Chile)

“…On the other hand, hair melanin content has been shown to affect the incorporation into hair of alkaline molecules such as alkaloids. Thus, basic molecules show significant in vitro affinity for melanin (Pötsch et al, 1997b;Claffey et al, 2001) and concentration of alkaline drugs in pigmented hair is higher than in non-pigmented hair (Uematsu et al, 1990;Sato et al, 1993;Mizuno et al, 1993;Rothe et al, 1997). The hair of natives from SPA (mummies as well as their present-day descendants) are black (with the exception of some older individuals whose hair is greyish), suggesting a capacity to accumulate alkaloids.…”

New trends in hair analysis and scientific demands on validation and technical notes

“…For in vivo studies results from pigmented and non-pigmented hair fibres are compared and striking differences in drug concentrations were found for various substances [21][22][23][24][25][26][27]. For in vitro studies investigation focuses on the interaction of various candidate drugs with synthetic melanin subtypes [28,29], melanin during its tyrosine-mediated formation [30] and melanin granules [31] as well as on the drug uptake in HaCaT and Sk-Mel-1 cells [32,33]. These cell lines maintain the expression and synthesis of keratin and melanin and may therefore serve as a model for long term drug exposure of the cell populations present in the anagen hair root.…”