PMID- 9097407
OWN - NLM
STAT- MEDLINE
DCOM- 19970627
LR  - 20161124
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 26
IP  - 1
DP  - 1997 May
TI  - A new iodinated tropane derivative (beta-CDIT) for in vivo dopamine transporter 
      exploration: comparison with beta-CIT.
PG  - 72-80
AB  - SPECT exploration of the dopamine transporter with tropane derivatives such as 
      beta-CIT has already produced very valuable information in humans. However, the 
      high affinity of this tracer for both dopamine and serotonin transporters and its 
      slow in vivo kinetics provide the best images in humans more than 20 h after 
      injection. In order to improve those properties, we performed structural changes 
      in the tropane structure in the phenyl and nitrogen substituents for higher 
      affinity and specificity and obtained a promising ligand, 2 beta-carbomethoxy-3 
      beta-(3',4' diclorophenyl)-8-(3-iodoprop-2E-enyl) nortropane (beta-CDIT). This 
      iodinated ligand was characterized in vitro and in vivo in the rat in comparison 
      with beta-CIT. In vitro competition studies revealed that beta-CIT and beta-CDIT 
      similarly inhibited the binding of [3H]GBR 12935 (Ki = 27.5 and 29.0 nM, 
      respectively). In contrast, competition studies with [3H]paroxetine and 
      [3H]nisoxetine showed that beta-CDIT had a lower affinity for the serotonin 
      transporter than beta-CIT (Ki = 50 and 3 nM, respectively) and also a lower 
      affinity for the noradrenaline transporter than beta-CIT (Ki = 500 and 80 nM, 
      respectively). In vivo studies in the rat showed that there was high and rapid 
      uptake of [125I] beta-CDIT in the striatum. In addition, preinjection of GBR 
      12909 prevented accumulation of this ligand in the striatum by 80%, whereas only 
      a 30% decrease was obtained for [125I] beta-CIT. It seems, therefore, that the 
      combination of aromatic and nitrogen substitution improves the properties of 
      tropane derivatives to provide an exclusive dopamine transporter ligand 
      potentially usable in SPECT.
FAU - Emond, P
AU  - Emond P
AD  - INSERM U316, Laboratoire de Biophysique Medicale et Pharmaceutique, Tours, 
      France.
FAU - Chalon, S
AU  - Chalon S
FAU - Garreau, L
AU  - Garreau L
FAU - Dognon, A M
AU  - Dognon AM
FAU - Bodard, S
AU  - Bodard S
FAU - Frangin, Y
AU  - Frangin Y
FAU - Baulieu, J L
AU  - Baulieu JL
FAU - Besnard, J C
AU  - Besnard JC
FAU - Guilloteau, D
AU  - Guilloteau D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Carrier Proteins)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 4H1Z7121WS (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects
MH  - Carrier Proteins/*drug effects
MH  - Cocaine/*analogs & derivatives/analysis/pharmacology
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Male
MH  - *Membrane Glycoproteins
MH  - *Membrane Transport Proteins
MH  - *Nerve Tissue Proteins
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Wistar
MH  - Tomography, Emission-Computed, Single-Photon
EDAT- 1997/05/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - 10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B [pii]
AID - 10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B [doi]
PST - ppublish
SO  - Synapse. 1997 May;26(1):72-80. doi: 
      10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B.