Synthesis, redox characteristics, and in vitro norepinephrine uptake inhibiting properties of 2-(2-mercapto-4,5-dihydroxyphenyl)ethylamine (6-mercaptodopamine).
In an attempt to further characterize the structural features of 6-hydroxydopamine analogues that are associated with in vivo neuronal degeneration, the synthesis of 6-mercaptodopamine was undertaken. Although reaction conditions leading to the 1,4 addition of thiols to the model quinone 4-methyl-o-benzoquinone were achieved, attempts to obtain 6-thiolated dopamine analogues by this route failed. The synthesis of 6-mercaptodopamine was achieved by the regioselective thiocyanation of O,O-dimethyldopamine, followed by bis-O-demethylation and reductive cleavage of the S-cyano group. Unlike 6-hydroxydopamine, 6-mercaptodopamine was resistant to autoxidation at pH 7.4. Cyclic voltammometric analysis, however, indicated that electrochemically generated oxidation species of 6-mercaptodopamine are unstable and undergo spontaneous reaction, presumably intramolecular cyclization. In vivo tests revealed that 6-mercaptodopamine inhibits the uptake of tritium-labeled norepinephrine by isolated rat heart atria, although to a much lesser extent than 6-hydroxydopamine.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004563:Electrochemistry; D006892:Hydroxydopamines; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
C024710:6-mercaptodopamine; D006892:Hydroxydopamines; D004298:Dopamine; D009638:Norepinephrine