Document Detail

Recovery of dopamine transporter binding and function after intrastriatal administration of the irreversible inhibitor RTI-76 [3 beta-(3p-chlorophenyl) tropan-2 beta-carboxylic acid p-isothiocyanatophenylethyl ester hydrochloride].
MedLine Citation:
PMID:  8858994     Owner:  NLM     Status:  MEDLINE    
Effects of in vivo, intrastriatal administration of RTI-76 ¿3 beta-(3-p-chlorophenyl) tropan-2 beta-carboxylic acid p-isothiocyanato-phenylethyl ester hydrochloride¿, an irreversible inhibitor of dopamine transporter (DAT) binding in vitro, on [125I]RTI-55 ¿3 beta-[4-iodophenyl]tropan-2 beta-carboxylic acid methyl ester tartrate¿ binding to striatal DAT in vitro were examined in male rats. Effects on [3H]DAT and D1 dopamine receptor binding in vitro after intrastriatal RTI-76 injection were also determined. One hour after direct intrastriatal injection, RTI-76 caused a dose-related increase in KD for [125I]RTI-55 binding in vitro in striatal tissue, without affecting transporter maximum binding (Bmax). In contrast, 24 hr after administration, RTI-76 caused a dose-related decrease in striatal DAT Bmax without affecting KD, a decrease that reversed over the next several days. Transport of [3H]dopamine into synaptosomes was decreased similarly. Intrastriatal injection of reversible inhibitors of DAT, such as cocaine or WIN-35428 ¿3 beta-[4-fluorophenyl]tropan-2 beta-carboxylic acid methyl ester tartrate), was without effect on transporter binding 1 and 6 days after administration. RTI-76 had little effect on [3H]SCH-23390 ¿R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine¿ binding 1 or 24 hr after intrastriatal injection, indicating at least some selectivity of RTI-76 for DAT. The RTI-76-induced decrease in Bmax, as well as the concurrent decrease in [3H]DAT, were reversible, with the T1/2 of transporter recovery estimated to be 6 days.
A E Fleckenstein; S Pögün; F I Carroll; M J Kuhar
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  279     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-11-18     Completed Date:  1996-11-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  200-6     Citation Subset:  IM    
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
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MeSH Terms
Carrier Proteins / antagonists & inhibitors*
Cocaine / analogs & derivatives,  metabolism
Corpus Striatum / metabolism*
Dopamine / metabolism
Dopamine Plasma Membrane Transport Proteins
Membrane Glycoproteins*
Membrane Transport Proteins*
Nerve Tissue Proteins*
Rats, Sprague-Dawley
Tropanes / pharmacology*
Reg. No./Substance:
0/Carrier Proteins; 0/Dopamine Plasma Membrane Transport Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/RTI 76; 0/Slc6a3 protein, rat; 0/Tropanes; 133647-95-7/RTI 55; 50-36-2/Cocaine; 50370-56-4/(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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