[3H]Threo‐(±)‐Methylphenidate Binding to 3,4‐Dihydroxyphenylethylamine Uptake Sites in Corpus Striatum: Correlation with the Stimulant Properties of Ritalinic Acid Esters

Margaret M. Schweri, Phil Skolnick, Michael F. Rafferty, Kenner C. Rice, Aaron J. Janowsky, Steven M. Paul

Research output: Research - peer-reviewArticle

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Abstract

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.

LanguageEnglish (US)
Pages1062-1070
Number of pages9
JournalJournal of Neurochemistry
Volume45
Issue number4
DOIs
StatePublished - 1985
Externally publishedYes

Fingerprint

ritalinic acid
Corpus Striatum
Methylphenidate
Esters
Binding Sites
Membranes
Dopamine
Synaptosomes
Psychotropic Drugs
Amines
Sodium
Ions
Brain
Proteins
Rats

Keywords

  • Dopamine up
  • Striatum
  • take stimulants
  • [H]Threo‐ (±)‐methylphenidate‐Ritalinic acid

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Cellular and Molecular Neuroscience

Cite this

[3H]Threo‐(±)‐Methylphenidate Binding to 3,4‐Dihydroxyphenylethylamine Uptake Sites in Corpus Striatum : Correlation with the Stimulant Properties of Ritalinic Acid Esters. / Schweri, Margaret M.; Skolnick, Phil; Rafferty, Michael F.; Rice, Kenner C.; Janowsky, Aaron J.; Paul, Steven M.

In: Journal of Neurochemistry, Vol. 45, No. 4, 1985, p. 1062-1070.

Research output: Research - peer-reviewArticle

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abstract = "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.",
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AU - Janowsky,Aaron J.

AU - Paul,Steven M.

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N2 - 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.

AB - 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.

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