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.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call