Binding of d-threo-[11C]methylphenidate to the dopamine transporter in vivo: insensitivity to synaptic dopamine

S. John Gatley, Yu Shin Ding, Nora D. Volkow, Ruoyan Chen, Yuichi Sugano, Joanna S. Fowler

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The regional distribution of [11C]d-threo-methylphenidate in mouse brain was very similar to that of [3H]WIN 35,428 ((-)-2β-carbomethoxy-3β-(4-fluorophenyl)tropane), and the two radioligands were displaced from striatum similarly after administration of the potent cocaine analog RTI-55 ((-)-2β-carbomethoxy-3β-(4-iodophenyl)tropane). However, while striatal [3H]WIN 35,428 increased between 5 and 30 min, striatal [11C]d-threo-methylphenidate halved. Thus [11C]d-threo-methylphenidate binds similarly to but more reversibly than [3H]WIN 35,428. The methyl ester of L-DOPA (l-3,4-dihydroxyphenylalanine; 200 mg/kg) plus benserazide plus clorgyline, which markedly elevates rat striatal extracellular dopamine (Wachtel and Abercrombie, 1994, J. Neurochem. 63, 108), decreased the mouse striatum-to-cerebellum ratio for [11C]d-threo-methylphenidate at 30 min by 13% (P < 0.05). In position emission tomographic (PET) baboon studies [11C]d-threo-methylphenidate binding was insensitive to drugs expected to lower endogenous dopamine. These experiments suggest that normal synaptic dopamine does not compete for binding with [11C]d-threo-methylphenidate, and will not affect PET measures of dopamine transporter availability.

Original languageEnglish
Pages (from-to)141-149
Number of pages9
JournalEuropean Journal of Pharmacology
Volume281
Issue number2
DOIs
StatePublished - 4 Aug 1995
Externally publishedYes

Keywords

  • (Baboon)
  • (Mouse)
  • Dopamine
  • Dopamine transporter
  • Methylphenidate
  • PET (positron emission tomography)
  • WIN 35,428
  • d-threo-Methylphenidate

Fingerprint

Dive into the research topics of 'Binding of d-threo-[11C]methylphenidate to the dopamine transporter in vivo: insensitivity to synaptic dopamine'. Together they form a unique fingerprint.

Cite this