title: [3H]Threo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters.
abstract: Saturable and stereoselective binding sites for [3H]threo-(+/-)-methylphenidate were characterized in rat brain membranes. The highest density of [3H]threo-(+/-)-methylphenidate binding sites was found in the synaptosomal fraction of corpus striatum. Scatchard analysis revealed a single class of noninteracting binding sites with an apparent dissociation constant (KD) of 235 nM and a maximum number of binding sites (Bmax) of 13.4 pmol/mg protein. Saturable, high-affinity binding of [3H]threo-(+/-)-methylphenidate to striatal synaptosomal membranes was dependent on the presence of sodium ions. A good correlation (r = 0.88; p less than 0.001) was observed between the potencies of various psychotropic drugs in displacing [3H]threo-(+/-)-methylphenidate from these sites and their potencies as inhibitors of [3H]3,4-dihydroxyphenylethylamine ( [3H]dopamine) uptake into striatal synaptosomes. A good correlation (r = 0.85; p less than 0.001) was also observed between the potencies of a series of ritalinic acid esters in inhibiting [3H]threo-(+/-)-methylphenidate binding to striatal synaptosomal membranes and their potencies as motor stimulants in mice. These observations suggest that the binding sites for [3H]threo-(+/-)-methylphenidate described here are associated with a dopamine uptake or transport complex, and that these sites may mediate the motor stimulant properties of ritalinic acid esters such as methylphenidate.
mesh_terms: D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005374:Filtration; D008297:Male; D008774:Methylphenidate / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D013237:Stereoisomerism; D013570:Synaptic Membranes / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D008774:Methylphenidate; D012965:Sodium Chloride; C009189:ritalinic acid; D004298:Dopamine