3H-nicotine, 3H-flunitrazepam, and 3H-cocaine incorporation into melanin: a model for the examination of drug-melanin interactions.
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.
Claffey
D J
DJ
University of Colorado Health Sciences Center, Molecular Toxicology and Environmental Health Sciences, Denver 80262, USA.
Stout
P R
PR
Ruth
J A
JA
D003042:Cocaine / Q000737:chemistry / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005445:Flunitrazepam / Q000737:chemistry / Q000493:pharmacokinetics*; D018757:GABA Modulators / Q000737:chemistry / Q000493:pharmacokinetics*; D005731:Ganglionic Stimulants / Q000737:chemistry / Q000493:pharmacokinetics*; D006197:Hair / Q000737:chemistry; D006801:Humans; D008543:Melanins / Q000737:chemistry*; D009294:Narcotics / Q000737:chemistry / Q000493:pharmacokinetics*; D009538:Nicotine / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers; D014316:Tritium / Q000493:pharmacokinetics
D018757:GABA Modulators; D005731:Ganglionic Stimulants; D008543:Melanins; D009294:Narcotics; D011108:Polymers; D014316:Tritium; D005445:Flunitrazepam; D009538:Nicotine; D003042:Cocaine