A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT
Identifieur interne : 001D64 ( Istex/Corpus ); précédent : 001D63; suivant : 001D65A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT
Auteurs : Patrick Emond ; Sylvie Chalon ; Lucette Garreau ; Anne-Marie Dognon ; Sylvie Bodard ; Yves Frangin ; Jean-Louis Baulieu ; Jean-Claude Besnard ; Dennis GuilloteauSource :
- Synapse [ 0887-4476 ] ; 1997-05.
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Abstract
SPECT exploration of the dopamine transporter with tropane derivatives such as β‐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, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐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 β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [125I] β‐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]β‐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. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.
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DOI: 10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B
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U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Chalon, Sylvie" sort="Chalon, Sylvie" uniqKey="Chalon S" first="Sylvie" last="Chalon">Sylvie Chalon</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Garreau, Lucette" sort="Garreau, Lucette" uniqKey="Garreau L" first="Lucette" last="Garreau">Lucette Garreau</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Dognon, Anne Arie" sort="Dognon, Anne Arie" uniqKey="Dognon A" first="Anne-Marie" last="Dognon">Anne-Marie Dognon</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Bodard, Sylvie" sort="Bodard, Sylvie" uniqKey="Bodard S" first="Sylvie" last="Bodard">Sylvie Bodard</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Frangin, Yves" sort="Frangin, Yves" uniqKey="Frangin Y" first="Yves" last="Frangin">Yves Frangin</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Baulieu, Jean Ouis" sort="Baulieu, Jean Ouis" uniqKey="Baulieu J" first="Jean-Louis" last="Baulieu">Jean-Louis Baulieu</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Besnard, Jean Laude" sort="Besnard, Jean Laude" uniqKey="Besnard J" first="Jean-Claude" last="Besnard">Jean-Claude Besnard</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation></author><author><name sortKey="Guilloteau, Dennis" sort="Guilloteau, Dennis" uniqKey="Guilloteau D" first="Dennis" last="Guilloteau">Dennis Guilloteau</name><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1997-05">1997-05</date><biblScope unit="volume">26</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="72">72</biblScope><biblScope unit="page" to="80">80</biblScope></imprint><idno type="ISSN">0887-4476</idno></series><idno type="istex">62A1AB80801BFA1B3C77F644B18676EE73CA6AFB</idno><idno type="DOI">10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B</idno><idno type="ArticleID">SYN8</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0887-4476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>SPECT</term><term>dopamine transporter</term><term>tropane derivative</term><term>β‐CIT</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">SPECT exploration of the dopamine transporter with tropane derivatives such as β‐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, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐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 β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [125I] β‐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]β‐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. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Patrick Emond</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Sylvie Chalon</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Lucette Garreau</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Anne‐Marie Dognon</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Sylvie Bodard</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Yves Frangin</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Jean‐Louis Baulieu</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Jean‐Claude Besnard</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string></affiliations></json:item><json:item><name>Dennis Guilloteau</name><affiliations><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</json:string><json:string>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>dopamine transporter</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>tropane derivative</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>β‐CIT</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SPECT</value></json:item></subject><articleId><json:string>SYN8</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>SPECT exploration of the dopamine transporter with tropane derivatives such as β‐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, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐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 β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [125I] β‐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]β‐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. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1674</abstractCharCount><pdfWordCount>5498</pdfWordCount><pdfCharCount>34302</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>252</abstractWordCount></qualityIndicators><title>A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT</title><refBibs><json:item><author><json:item><name>P. Abraham</name></json:item><json:item><name>J. B. Pitner</name></json:item><json:item><name>A. H. Lewin</name></json:item><json:item><name>J. W. Boja</name></json:item><json:item><name>M. J. Kuhar</name></json:item><json:item><name>F. I. Carroll</name></json:item></author><host><volume>35</volume><pages><last>144</last><first>141</first></pages><author></author><title>J. Med. 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Med.</title></host><title>Simplified multidose preparation of iodine‐123‐β‐CIT: A marker for dopamine transporter</title></json:item></refBibs><genre><json:string>article</json:string></genre><host><volume>26</volume><publisherId><json:string>SYN</json:string></publisherId><pages><total>9</total><last>80</last><first>72</first></pages><issn><json:string>0887-4476</json:string></issn><issue>1</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1098-2396</json:string></eissn><title>Synapse</title><doi><json:string>10.1002/(ISSN)1098-2396</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>neurosciences</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix></categories><publicationDate>1997</publicationDate><copyrightDate>1997</copyrightDate><doi><json:string>10.1002/(SICI)1098-2396(199705)26:1>72::AID-SYN8>3.0.CO;2-B</json:string></doi><id>62A1AB80801BFA1B3C77F644B18676EE73CA6AFB</id><score>0.20289937</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/62A1AB80801BFA1B3C77F644B18676EE73CA6AFB/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/62A1AB80801BFA1B3C77F644B18676EE73CA6AFB/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/62A1AB80801BFA1B3C77F644B18676EE73CA6AFB/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><availability><p>Copyright © 1997 Wiley‐Liss, Inc.</p></availability><date>1997</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT</title><author xml:id="author-1"><persName><forename type="first">Patrick</forename><surname>Emond</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">Sylvie</forename><surname>Chalon</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-3"><persName><forename type="first">Lucette</forename><surname>Garreau</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">Anne‐Marie</forename><surname>Dognon</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">Sylvie</forename><surname>Bodard</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Yves</forename><surname>Frangin</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Jean‐Louis</forename><surname>Baulieu</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-8"><persName><forename type="first">Jean‐Claude</forename><surname>Besnard</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation></author><author xml:id="author-9"><persName><forename type="first">Dennis</forename><surname>Guilloteau</surname></persName><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France</affiliation></author></analytic><monogr><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="pISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><idno type="DOI">10.1002/(ISSN)1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1997-05"></date><biblScope unit="volume">26</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="72">72</biblScope><biblScope unit="page" to="80">80</biblScope></imprint></monogr><idno type="istex">62A1AB80801BFA1B3C77F644B18676EE73CA6AFB</idno><idno type="DOI">10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B</idno><idno type="ArticleID">SYN8</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1997</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>SPECT exploration of the dopamine transporter with tropane derivatives such as β‐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, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐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 β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [125I] β‐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]β‐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. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>dopamine transporter</term></item><item><term>tropane derivative</term></item><item><term>β‐CIT</term></item><item><term>SPECT</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1996-01-25">Received</change><change when="1996-10-03">Registration</change><change when="1997-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/62A1AB80801BFA1B3C77F644B18676EE73CA6AFB/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>John Wiley & Sons, Inc.</publisherName><publisherLoc>New York</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1098-2396</doi><issn type="print">0887-4476</issn><issn type="electronic">1098-2396</issn><idGroup><id type="product" value="SYN"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="SYNAPSE">Synapse</title><title type="short">Synapse</title></titleGroup></publicationMeta><publicationMeta level="part" position="10"><doi origin="wiley" registered="yes">10.1002/(SICI)1098-2396(199705)26:1<>1.0.CO;2-F</doi><numberingGroup><numbering type="journalVolume" number="26">26</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="1997-05">May 1997</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="8" status="forIssue"><doi origin="wiley" registered="yes">10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B</doi><idGroup><id type="unit" value="SYN8"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><copyright ownership="publisher">Copyright © 1997 Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="1996-01-25"></event><event type="manuscriptAccepted" date="1996-10-03"></event><event type="firstOnline" date="1998-12-07"></event><event type="publishedOnlineFinalForm" date="1998-12-07"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-04"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-10"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-11-03"></event></eventGroup><numberingGroup><numbering type="pageFirst">72</numbering><numbering type="pageLast">80</numbering></numberingGroup><correspondenceTo>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:SYN.SYN8.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="37"></count></countGroup><titleGroup><title type="main" xml:lang="en">A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Patrick</givenNames><familyName>Emond</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Sylvie</givenNames><familyName>Chalon</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Lucette</givenNames><familyName>Garreau</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Anne‐Marie</givenNames><familyName>Dognon</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Sylvie</givenNames><familyName>Bodard</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Yves</givenNames><familyName>Frangin</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jean‐Louis</givenNames><familyName>Baulieu</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jean‐Claude</givenNames><familyName>Besnard</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Dennis</givenNames><familyName>Guilloteau</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">dopamine transporter</keyword><keyword xml:id="kwd2">tropane derivative</keyword><keyword xml:id="kwd3">β‐CIT</keyword><keyword xml:id="kwd4">SPECT</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>SPECT exploration of the dopamine transporter with tropane derivatives such as β‐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, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐CDIT similarly inhibited the binding of [<sup>3</sup>H]GBR 12935 (Ki = 27.5 and 29.0 nM, respectively). In contrast, competition studies with [<sup>3</sup>H]paroxetine and [<sup>3</sup>H]nisoxetine showed that β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [<sup>125</sup>I] β‐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 [<sup>125</sup>I]β‐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. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT</title></titleInfo><name type="personal"><namePart type="given">Patrick</namePart><namePart type="family">Emond</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sylvie</namePart><namePart type="family">Chalon</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lucette</namePart><namePart type="family">Garreau</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anne‐Marie</namePart><namePart type="family">Dognon</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sylvie</namePart><namePart type="family">Bodard</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yves</namePart><namePart type="family">Frangin</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Louis</namePart><namePart type="family">Baulieu</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Claude</namePart><namePart type="family">Besnard</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dennis</namePart><namePart type="family">Guilloteau</namePart><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 37200 Tours, France</affiliation><affiliation>INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">1997-05</dateIssued><dateCaptured encoding="w3cdtf">1996-01-25</dateCaptured><dateValid encoding="w3cdtf">1996-10-03</dateValid><copyrightDate encoding="w3cdtf">1997</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">3</extent><extent unit="references">37</extent></physicalDescription><abstract lang="en">SPECT exploration of the dopamine transporter with tropane derivatives such as β‐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, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐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 β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [125I] β‐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]β‐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. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.</abstract><subject lang="en"><genre>keywords</genre><topic>dopamine transporter</topic><topic>tropane derivative</topic><topic>β‐CIT</topic><topic>SPECT</topic></subject><relatedItem type="host"><titleInfo><title>Synapse</title></titleInfo><titleInfo type="abbreviated"><title>Synapse</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0887-4476</identifier><identifier type="eISSN">1098-2396</identifier><identifier type="DOI">10.1002/(ISSN)1098-2396</identifier><identifier type="PublisherID">SYN</identifier><part><date>1997</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>72</start><end>80</end><total>9</total></extent></part></relatedItem><identifier type="istex">62A1AB80801BFA1B3C77F644B18676EE73CA6AFB</identifier><identifier type="DOI">10.1002/(SICI)1098-2396(199705)26:1<72::AID-SYN8>3.0.CO;2-B</identifier><identifier type="ArticleID">SYN8</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1997 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>John Wiley & Sons, Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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