Article

Comparison between dopamine transporter affinity and self-administration potency of local anesthetics in rhesus monkeys.

The University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Jackson 39216, USA.
European Journal of Pharmacology (Impact Factor: 2.68). 02/1999; 367(2-3):175-81. DOI: 10.1016/S0014-2999(98)00967-4
Source: PubMed

ABSTRACT Local anesthetics bind to dopamine transporters and inhibit dopamine uptake in rodent brain. Additionally, local anesthetics are self-administered in rhesus monkeys. The present study determined binding affinities of cocaine and five local anesthetics at dopamine transporters in rhesus monkey brain, and compared binding affinities to published self-administration potencies in rhesus monkeys. The affinity order at dopamine transporters was cocaine > dimethocaine > tetracaine > procaine > or = chloroprocaine > lidocaine. The correlation between dopamine transporter affinities and self-administration potencies was significant. Binding affinities were also determined at sodium (Na2+) channels in rhesus monkey brain. There was not a significant correlation between Na2+ channel affinities and self-administration potencies Local anesthetics with high dopamine transporter and low Na2+ channel affinities were self-administered, whereas those with either high or low affinity at both sites were not consistently self-administered. These data suggest that affinity at dopamine transporters is related to the reinforcing effects of local anesthetics in rhesus monkeys, and Na2+ channel effects may interfere with the reinforcing effect of these drugs.

0 Bookmarks
 · 
59 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate (Vmax ) of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc. Synapse, 2014. © 2014 Wiley Periodicals, Inc.
    Synapse 06/2014; · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: (S)-(+)-1-(4-{2-[Bis-(4-fluorophenyl)methoxy]-ethyl}piperazin-1-yl)-2-phenylpropan-2-ol dimaleate was prepared in several steps from (S)-(+)-atrolactic acid by a process permitting synthesis of multigram quantities. With the information provided by asymmetric synthesis, the X-ray crystal structure was solved.
    Tetrahedron Asymmetry 10/2003; 14(21):3285-3289. · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: KE YWORDS dopamin etransporters ;transporte roccupancy ;PET ;tissu ereference method ABSTRACT Th efractio no ftransporter soccupie dfollowin ginjectio no fspecifi cin- hibitor si sa nimportan tparamete rfo rdefinin gan dcomparin gth emolecula rmecha- nism so fdifferen tdrugs .Thi swor kgeneralize sth ereferenc etissu emetho dt oestimate dopamin etransporte roccupanc yfo rtw olevel so fcocain eadministratio nusin gonl ya singl einjectio no f(18F)FECNT .Th eresult sar evalidate db ycompariso nwit hliterature values .Fiv erhesu smonkey swer estudied .O neac hanimal ,a baselin esca nwas collecte dfollowin g(18F)FECN Tinjectio n(phas ea) .A t12 0mi npostinjection ,0. 1mg/kg cocain ewa sinjecte dan dth eanima lwa sscanne dfo r5 0additiona lmi n(phas eb) .Then 1. 0mg/k gcocain ewa sinjecte dan danothe r50-mi nsca nsequenc ewa scollecte d(phase c) .Time-activit ycurve s(encompassin gal lthre ephases )wer egenerate dfo reac hanimal fro mregion sdraw nove rth eputame nan dcerebellum .Th eputame ncurv ewa smodeled usin gth ecerebellu ma sth einpu tfunction .Percen tDA Toccupanc yfollowin gth ecocaine injection swa sdetermine db ycomparin gk3/k4 Bmax/kD fo rth ethre ephases .Th e0.1 an d1. 0mg/k gcocain edose soccupie d53 % 5 %an d87 % 5 %o fth etransporters, respectively .Th emeasure doccupancie sar econsisten twit hliteratur evalue stha tmain- tai nself-administratio ni nanimal san dproduc ea "high "i nhuma nsubjects .Thi swork demonstrate stha t asingl einjectio no f(18F)FECN Tca nb euse dt omeasur eth eeffects o fmultipl ecocain echallenges .Tw oadvantage so fthi stechniqu eare :reduce dvariability i ndose-respons ecurve sbecaus eth esubjec ti shis/he row ncontrol ,an dthe 18 Flabel allow sevaluatio no flonger-actin gdrugs .Synaps e44:203-210 ,2002. ©200 2Wiley-Liss ,Inc.