188680-64-0Relevant articles and documents
N-(3-lodoprop-2E-enyl)-2β-carbomethoxy-3β-(3',4'- dichlorophenyl)nortropane (β-CDIT), a tropane derivative: Pharmacological characterization as a specific ligand for the dopamine transporter in the rodent brain
Garreau, Lucette,Emond, Patrick,Belzung, Catherine,Guilloteau, Denis,Frangin, Yves,Besnard, Jean-Claude,Chalon, Sylvie
, p. 467 - 474 (2007/10/03)
N-(3-lodoprop-2E-enyl)-2β-carbomethoxy-3β-(3',4'- dichlorophenyl)nortropane (β-CDIT), a new iodinated tropane derivative, has been synthesized and radiolabeled with iodine. [125I]β-CDIT was tested in vitro and ex vivo as a probe for the dopamine transporter site in the rat brain, and behavioral studies were performed in mice. Saturation studies in the striatum revealed that [125I]β-CDIT bound to a single high-affinity site. The K(d) value was 0.18 ± 0.07 nM, and the corresponding B(max) value was 500 ± 80 fmol/mg of protein. The pharmacological profile of specific [125I]β-CDIT binding in the striatum was consistent with that of the dopamine transporter. In addition, competition studies in cerebral cortex regions with [3H]paroxetine and [3H]nisoxetine showed a very low affinity of β-CDIT for the 5-hydroxytryptamine (K(i) = 50 nM) and norepinephrine (K(i) = 500 nM) transporters compared with β-CIT (corresponding K(i) values were 3 and 80 nM). In contrast, the competition of β-CDIT with [3H]GBR 12935 in the striatal region (K(i) = 29 nM) was of the same order of value as for β-CIT (K(i) = 27.5 nM). Behavioral experiments in mice showed that both β-CDIT and β-CIT induced stimulation of locomotor activity. Ex vivo autoradiographic studies in rats using [125I]β-CDIT demonstrated high densities of [125I]β-CDIT binding sites in areas known to be rich in dopaminergic innervation. Because of its high affinity and high selectivity for the dopamine transporter, [125I]β-CDIT should be a valuable ligand for the exploration of the dopamine transporter with single-photon emission computed tomography.
