Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor
Identifieur interne : 004863 ( Main/Merge ); précédent : 004862; suivant : 004864Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor
Auteurs : Fredricka C. Martin [États-Unis] ; Adrian Handforth [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2006-10.
English descriptors
- KwdEn :
- 1-Octanol (pharmacology), Animals, Carbenoxolone (pharmacology), Central Nervous System Stimulants, Cerebellum (drug effects), Chloroquine (pharmacology), Connexins (metabolism), Disease Models, Animal, Dose-Response Relationship, Drug, Essential Tremor (chemically induced), Essential Tremor (physiopathology), Female, Gap Junctions (drug effects), Glycyrrhizic Acid (pharmacology), Harmaline, Heptanol (pharmacology), Injections, Subcutaneous, Mefloquine (pharmacology), Mice, Mice, Inbred ICR, Olivary Nucleus (drug effects), carbenoxolone, connexin, essential tremor, gap junction, harmaline, mefloquine.
- MESH :
- chemical , metabolism : Connexins.
- chemical , pharmacology : 1-Octanol, Carbenoxolone, Chloroquine, Glycyrrhizic Acid, Heptanol, Mefloquine.
- chemically induced : Essential Tremor.
- drug effects : Cerebellum, Gap Junctions, Olivary Nucleus.
- physiopathology : Essential Tremor.
- Animals, Central Nervous System Stimulants, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Harmaline, Injections, Subcutaneous, Mice, Mice, Inbred ICR.
Abstract
Excessive olivo‐cerebellar synchrony is implicated in essential tremor. Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open‐treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg/kg s.c. In mice the broad‐spectrum gap junction blockers heptanol, octanol (350 mg/kg i.p. each), and carbenoxolone (20 mg/kg) suppressed harmaline tremor. Mefloquine (50 mg/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti‐tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36. © 2006 Movement Disorder Society
Url:
DOI: 10.1002/mds.20940
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Martin</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Handforth, Adrian" sort="Handforth, Adrian" uniqKey="Handforth A" first="Adrian" last="Handforth">Adrian Handforth</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurology Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. 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Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open‐treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg/kg s.c. In mice the broad‐spectrum gap junction blockers heptanol, octanol (350 mg/kg i.p. each), and carbenoxolone (20 mg/kg) suppressed harmaline tremor. Mefloquine (50 mg/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti‐tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36. © 2006 Movement Disorder Society</div></front></TEI><double doi="10.1002/mds.20940"><ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor</title><author><name sortKey="Martin, Fredricka C" sort="Martin, Fredricka C" uniqKey="Martin F" first="Fredricka C." last="Martin">Fredricka C. Martin</name></author><author><name sortKey="Handforth, Adrian" sort="Handforth, Adrian" uniqKey="Handforth A" first="Adrian" last="Handforth">Adrian Handforth</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0E60A7979FB53CAB9A9D21829364F25E081D73A6</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1002/mds.20940</idno><idno type="url">https://api.istex.fr/document/0E60A7979FB53CAB9A9D21829364F25E081D73A6/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000578</idno><idno type="wicri:Area/Istex/Curation">000578</idno><idno type="wicri:Area/Istex/Checkpoint">002009</idno><idno type="wicri:doubleKey">0885-3185:2006:Martin F:carbenoxolone:and:mefloquine</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor</title><author><name sortKey="Martin, Fredricka C" sort="Martin, Fredricka C" uniqKey="Martin F" first="Fredricka C." last="Martin">Fredricka C. Martin</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Handforth, Adrian" sort="Handforth, Adrian" uniqKey="Handforth A" first="Adrian" last="Handforth">Adrian Handforth</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurology Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2006-10">2006-10</date><biblScope unit="vol">21</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1641">1641</biblScope><biblScope unit="page" to="1649">1649</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">0E60A7979FB53CAB9A9D21829364F25E081D73A6</idno><idno type="DOI">10.1002/mds.20940</idno><idno type="ArticleID">MDS20940</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>carbenoxolone</term><term>connexin</term><term>essential tremor</term><term>gap junction</term><term>harmaline</term><term>mefloquine</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Excessive olivo‐cerebellar synchrony is implicated in essential tremor. Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open‐treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg/kg s.c. In mice the broad‐spectrum gap junction blockers heptanol, octanol (350 mg/kg i.p. each), and carbenoxolone (20 mg/kg) suppressed harmaline tremor. Mefloquine (50 mg/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti‐tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36. © 2006 Movement Disorder Society</div></front></TEI></ISTEX><PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor.</title><author><name sortKey="Martin, Fredricka C" sort="Martin, Fredricka C" uniqKey="Martin F" first="Fredricka C" last="Martin">Fredricka C. Martin</name><affiliation wicri:level="2"><nlm:affiliation>Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Handforth, Adrian" sort="Handforth, Adrian" uniqKey="Handforth A" first="Adrian" last="Handforth">Adrian Handforth</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="doi">10.1002/mds.20940</idno><idno type="RBID">pubmed:16773639</idno><idno type="pmid">16773639</idno><idno type="wicri:Area/PubMed/Corpus">002B92</idno><idno type="wicri:Area/PubMed/Curation">002B92</idno><idno type="wicri:Area/PubMed/Checkpoint">002E37</idno><idno type="wicri:Area/Ncbi/Merge">001744</idno><idno type="wicri:Area/Ncbi/Curation">001744</idno><idno type="wicri:Area/Ncbi/Checkpoint">001744</idno><idno type="wicri:doubleKey">0885-3185:2006:Martin F:carbenoxolone:and:mefloquine</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor.</title><author><name sortKey="Martin, Fredricka C" sort="Martin, Fredricka C" uniqKey="Martin F" first="Fredricka C" last="Martin">Fredricka C. Martin</name><affiliation wicri:level="2"><nlm:affiliation>Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Handforth, Adrian" sort="Handforth, Adrian" uniqKey="Handforth A" first="Adrian" last="Handforth">Adrian Handforth</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Octanol (pharmacology)</term><term>Animals</term><term>Carbenoxolone (pharmacology)</term><term>Central Nervous System Stimulants</term><term>Cerebellum (drug effects)</term><term>Chloroquine (pharmacology)</term><term>Connexins (metabolism)</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Essential Tremor (chemically induced)</term><term>Essential Tremor (physiopathology)</term><term>Female</term><term>Gap Junctions (drug effects)</term><term>Glycyrrhizic Acid (pharmacology)</term><term>Harmaline</term><term>Heptanol (pharmacology)</term><term>Injections, Subcutaneous</term><term>Mefloquine (pharmacology)</term><term>Mice</term><term>Mice, Inbred ICR</term><term>Olivary Nucleus (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Connexins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Octanol</term><term>Carbenoxolone</term><term>Chloroquine</term><term>Glycyrrhizic Acid</term><term>Heptanol</term><term>Mefloquine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Essential Tremor</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cerebellum</term><term>Gap Junctions</term><term>Olivary Nucleus</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Essential Tremor</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Central Nervous System Stimulants</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Harmaline</term><term>Injections, Subcutaneous</term><term>Mice</term><term>Mice, Inbred ICR</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Excessive olivo-cerebellar synchrony is implicated in essential tremor. Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open-treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg/kg s.c. In mice the broad-spectrum gap junction blockers heptanol, octanol (350 mg/kg i.p. each), and carbenoxolone (20 mg/kg) suppressed harmaline tremor. Mefloquine (50 mg/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti-tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36.</div></front></TEI></PubMed></double></record>Pour manipuler ce document sous Unix (Dilib)
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