ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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 synapto somal 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 〈 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-dihydroxyphenylethyl- amine ([3H]dopamine) uptake into striatal synaptosomes. A good correlation (r = 0.85; p 〈 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-(±)-methyl-phenidate 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1985.tb05524.x
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