Pardoprunox reverses motor deficits but induces only mild dyskinesia in MPTP‐treated common marmosets
Identifieur interne : 000603 ( Main/Exploration ); précédent : 000602; suivant : 000604Pardoprunox reverses motor deficits but induces only mild dyskinesia in MPTP‐treated common marmosets
Auteurs : Louisa Clare Johnston [Royaume-Uni] ; Michael John Jackson [Royaume-Uni] ; Sarah Rose [Royaume-Uni] ; Andrew Christopher Mccreary [Pays-Bas] ; Peter Jenner [Royaume-Uni]Source :
- Movement Disorders [ 0885-3185 ] ; 2010-10-15.
English descriptors
Abstract
Long‐acting full dopamine D2 agonists produce less dyskinesia in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates and in Parkinson's disease than effective antiparkinsonian doses of levodopa. They do not however, prevent priming for dyskinesia expression on subsequent levodopa exposure. In contrast, the effects of partial D2 receptor agonists on dyskinesia are unclear. We now examine the ability of the partial D2 agonist pardoprunox (SLV308) to improve motor function and its propensity to prime for dyskinesia in drug naïve, MPTP‐treated common marmosets. Previously, drug naïve, MPTP‐treated common marmosets were treated with equivalent doses of either pardoprunox (SLV308) (0.1 mg/kg po), ropinirole (0.18 mg/kg po), or levodopa (10 mg/kg po BID) for 28 days. All treatments induced a similar reduction of motor disability. Dyskinesia induced by levodopa was of greater intensity than that following administration of either pardoprunox (SLV308) or ropinirole. Administration of pardoprunox (SLV308) resulted in dyskinesia that was less intense and of shorter duration than either ropinirole or levodopa. At the end of drug treatment, acute challenge with levodopa resulted in the expression of marked dyskinesia in animals that had previously received chronic levodopa or ropinirole treatment. However, animals previously treated with pardoprunox (SLV308) showed only mild dyskinesia in response to the levodopa challenge. These results suggest that the partial D2 agonist pardoprunox (SLV308) is less likely to prime for dyskinesia or to lead to the expression of dyskinesia than either levodopa or full dopamine agonists. © 2010 Movement Disorder Society
Url:
DOI: 10.1002/mds.23249
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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="2010-10-15">2010-10-15</date><biblScope unit="volume">25</biblScope><biblScope unit="issue">13</biblScope><biblScope unit="page" from="2059">2059</biblScope><biblScope unit="page" to="2066">2066</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">2113A8D24FCE723BD8E69F9D2D48F046F73F105C</idno><idno type="DOI">10.1002/mds.23249</idno><idno type="ArticleID">MDS23249</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>MPTP</term><term>Parkinson's disease</term><term>dyskinesia</term><term>levodopa</term><term>pardoprunox (SLV308)</term><term>partial agonist</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Long‐acting full dopamine D2 agonists produce less dyskinesia in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates and in Parkinson's disease than effective antiparkinsonian doses of levodopa. They do not however, prevent priming for dyskinesia expression on subsequent levodopa exposure. In contrast, the effects of partial D2 receptor agonists on dyskinesia are unclear. We now examine the ability of the partial D2 agonist pardoprunox (SLV308) to improve motor function and its propensity to prime for dyskinesia in drug naïve, MPTP‐treated common marmosets. Previously, drug naïve, MPTP‐treated common marmosets were treated with equivalent doses of either pardoprunox (SLV308) (0.1 mg/kg po), ropinirole (0.18 mg/kg po), or levodopa (10 mg/kg po BID) for 28 days. All treatments induced a similar reduction of motor disability. Dyskinesia induced by levodopa was of greater intensity than that following administration of either pardoprunox (SLV308) or ropinirole. Administration of pardoprunox (SLV308) resulted in dyskinesia that was less intense and of shorter duration than either ropinirole or levodopa. At the end of drug treatment, acute challenge with levodopa resulted in the expression of marked dyskinesia in animals that had previously received chronic levodopa or ropinirole treatment. However, animals previously treated with pardoprunox (SLV308) showed only mild dyskinesia in response to the levodopa challenge. These results suggest that the partial D2 agonist pardoprunox (SLV308) is less likely to prime for dyskinesia or to lead to the expression of dyskinesia than either levodopa or full dopamine agonists. © 2010 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Johnston, Louisa Clare" sort="Johnston, Louisa Clare" uniqKey="Johnston L" first="Louisa Clare" last="Johnston">Louisa Clare Johnston</name></region><name sortKey="Jackson, Michael John" sort="Jackson, Michael John" uniqKey="Jackson M" first="Michael John" last="Jackson">Michael John Jackson</name><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name><name sortKey="Rose, Sarah" sort="Rose, Sarah" uniqKey="Rose S" first="Sarah" last="Rose">Sarah Rose</name></country><country name="Pays-Bas"><noRegion><name sortKey="Mccreary, Andrew Christopher" sort="Mccreary, Andrew Christopher" uniqKey="Mccreary A" first="Andrew Christopher" last="Mccreary">Andrew Christopher Mccreary</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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