title: Methylphenidate analogs with behavioral differences interact differently with arginine residues on the dopamine transporter in rat striatum.
abstract: The methylphenidate analogs N-methyl-4-methyl-methylphenidate and N-benzylmethylphenidate are believed to interact differently with the dopamine transporter (DAT) in vitro and in vivo. Herein, we report that methylphenidate and N-methyl-4-methyl-methylphenidate, but not N-benzylmethylphenidate, protect the rat striatal DAT from the arginine-selective chemical modifying agent, phenylglyoxal. This suggests that methylphenidate and N-methyl-4-methyl-methylphenidate, but not N-benzylmethylphenidate, interact with the guanidine groups of arginine residues in the DAT of rat striatum. This differential interaction may, at least in part, explain the in vitro and in vivo differences between N-methyl-4-methyl-methylphenidate and N-benzylmethylphenidate.
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington 99164-4630, USA.
authors.forename: Trent J
authors.initials: TJ
authors.lastname: Volz
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Bjorklund
authors.forename: James O
authors.initials: JO
authors.lastname: Schenk
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008774:Methylphenidate / Q000031:analogs & derivatives / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010655:Phenylenediamines / Q000494:pharmacology; D010658:Phenylglyoxal / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C452341:N-methylphenyl-N'-methylphenyl-p-phenylenediamine; D009419:Nerve Tissue Proteins; D010655:Phenylenediamines; C493216:Slc6a3 protein, rat; D008774:Methylphenidate; D001120:Arginine; D010658:Phenylglyoxal; D015655:1-Methyl-4-phenylpyridinium