title: Studies on the melanin affinity of selegiline (deprenyl) and other amphetamine derivatives.
abstract: The main aim of our study was to assess the melanin affinity of selegiline as well as the pharmacologic and pharmacokinetic aspects of its binding. The in vivo melanin binding of [14C] selegiline was studied by the method of whole body autoradiography. Extensive accumulation was observed in the pigmented mouse eye while in the albino animal uptake was low in the corresponding tissues. Our in vitro investigations demonstrated that the amphetamine derivatives tested can be taken up by melanins. Scatchard analysis of selegiline binding to the dopamine melanin (structurally similar to the neuromelanin) and beef eye melanin showed that more than one class of binding sites may be implicated. The total binding capacity of the beef-eye melanin was higher than that of the dopamine melanin. The selegiline inhibition of the [3H] MPP+ (the neurotoxic metabolite of MPTP) binding to dopamine melanin was also investigated. In the studied concentration range, the binding of [3H] MPP+ was depressed to about 70 per cent of the original maximum value. In conclusion, as a result of its melanin affinity, which is demonstrated in this study, selegiline may most probably accumulate in the pigmented nerve cells. The observed melanin affinity may contribute to the application of this compound for the treatment of Parkinson's disease or may play a role in its protective effect against MPTP neurotoxicity.
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D008297:Male; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010627:Phenethylamines / Q000493:pharmacokinetics*; D011726:Pyridinium Compounds / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000493:pharmacokinetics*
chemical_list: D008543:Melanins; D010627:Phenethylamines; D011726:Pyridinium Compounds; D011954:Receptors, Dopamine; D012642:Selegiline; C026560:1-(4-methoxyphenyl)pyridinium; D000661:Amphetamine