+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Methyl 3-beta- iodophenyl tropane-2-beta-carboxylate in vitro binding to dopamine and serotonin transporters under physiological conditions



Methyl 3-beta- iodophenyl tropane-2-beta-carboxylate in vitro binding to dopamine and serotonin transporters under physiological conditions



Journal of Neurochemistry 62(3): 978-986



Methyl 3-beta-(4-(125I)iodophenyl)tropane-2-beta-carboxylate ((123I)beta-CIT) is a single photon emission computed tomographic radiotracer for in vivo labeling of dopamine (DA) and serotonin (5-HT) transporters. Single photon emission computed tomographic experiments in nonhuman primates showed that (123I)beta-CIT in vivo binding to DA transporters had a much slower washout than binding to 5-HT transporters. This observation was not predicted from previously published in vitro studies. These studies, performed at 22 degree C in nonphysiological buffer, reported similar affinity of (125I)beta-CIT for DA and 5-HT transporters. We now report (125I)beta-CIT binding parameters to fresh rat membranes at 22 degree C and 37 degree C, in a buffer mimicking the composition of cerebrospinal fluid. At both temperatures, binding to DA transporters was best fit by a two-site model, whereas binding to 5-HT transporters was compatible with one population of sites. At 22 degree C, (125I)beta-CIT showed similar affinity to high-affinity DA (0.39 nM) and 5-HT transporter sites (0.47 nM). Increasing the incubation temperature from 22 degree C to 37 degree C reduced binding to DA transporters by 60%, whereas binding to 5-HT transporters was only marginally affected. In vitro kinetic experiments failed to detect significant differences in on or off rates that could explain the observed in vivo kinetics. These experiments thus failed to explain (123I)beta-CIT in vivo uptake kinetics, suggesting the existence of specific factors affecting the in vivo situation.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 032329943

Download citation: RISBibTeXText

PMID: 8113817


Related references

Binding of the cocaine analog 2 beta-carbomethoxy-3 beta-(4-[125I]iodophenyl)tropane to serotonin and dopamine transporters: different ionic requirements for substrate and 2 beta-carbomethoxy-3 beta-(4-[125I]iodophenyl)tropane binding. Molecular Pharmacology 43(2): 264-270, 1993

Long-lasting inhibition of in vivo cocaine binding to dopamine transporters by 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester: RTI-55 or beta CIT. Synapse 19(3): 206-211, 1995

N-substituted analogs of 2 beta-carbomethoxy-3 beta- (4'-iodophenyl)tropane (beta-CIT) with selective affinity to dopamine or serotonin transporters in rat forebrain. Journal of Medicinal Chemistry 39(2): 543-548, 1996

Enantioselectivity of cocaine recognition sites: binding of (1S)- and (1R)-2.beta.-carbomethoxy-3.beta.-(4-iodophenyl)tropane (.beta.-Cit) to monoamine transporters. Journal of Medicinal Chemistry 36(13): 1914-1917, 1993

Enantioselectivity of cocaine recognition sites: binding of (1S)- and (1R)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) to monoamine transporters. Journal of Medicinal Chemistry 36(13): 1914-1917, 1993

Evaluation of the monoamine uptake site ligand [123I]methyl 3 beta-(4-iodophenyl)-tropane-2 beta-carboxylate ([123I]beta-CIT) in non-human primates: pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI. Nuclear Medicine and Biology 20(5): 597-606, 1993

Comparison of iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane for imaging of the dopamine transporter in the living human brain. European Journal of Nuclear Medicine 22(4): 356-360, 1995

N-.omega.-Fluoroalkyl Analogs of (1R)-2.beta.-Carbomethoxy-3.beta.-(4-iodophenyl)tropane (.beta.-Cit): Radiotracers for Positron Emission Tomography and Single Photon Emission Computed Tomography Imaging of Dopamine Transporters. Journal of Medicinal Chemistry 37(11): 1558-1561, 1994

N-omega-fluoroalkyl analogs of (1R)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-tropane (beta-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. Journal of Medicinal Chemistry 37(11): 1558-1561, 1994

Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-beta-(4-iodophenyl)-tropane SPECT. Journal of Nuclear Medicine 49(5): 757-763, 2008

Seasonal variation of availability of serotonin transporter binding sites in healthy female subjects as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biological Psychiatry 47(2): 158-160, 2000

In vitro autoradiographic characterization of 3 beta 4 iodophenyltropane 2 beta carboxylic acid methyl iodine 125 rii 55 binding to dopamine and serotonin uptake site in rat brain. Society for Neuroscience Abstracts 17(1-2): 155, 1991

Synthesis of 3-beta substituted tropane-2-beta-carboxylic acid methyl esters as inhibitors of cocaine binding and dopamine uptake. Abstracts of Papers American Chemical Society 207(1-2): MEDI 169, 1994

Effect of the haloperidol tetrahydropyridine metabolite 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)-1,2,3,6-tetrahydropyridine on dopamine receptor and transporter binding: A nonhuman primate 123I-iodobenzamide and 2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane single photon emission computed tomographic study. Arzneimittel Forschung 47(6): 692-699, 1997

Effect of the haloperidol tetrahydropyridine metabolite 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine on dopamine receptor and transporter binding. A nonhuman primate 123I-iodobenzamide and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane single photon emission computed tomographic study. Arzneimittel-Forschung 47(6): 692-699, 1997