Synergistic antidyskinetic effects of topiramate and amantadine in animal models of Parkinson's disease
Identifieur interne : 001363 ( Main/Exploration ); précédent : 001362; suivant : 001364Synergistic antidyskinetic effects of topiramate and amantadine in animal models of Parkinson's disease
Auteurs : Christopher Kobylecki [Royaume-Uni] ; Michael P. Hill [Canada] ; Alan R. Crossman [Royaume-Uni] ; Paula Ravenscroft [Royaume-Uni, Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 2011-11.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- 6‐OHDA‐lesioned rat, Amantadine, Amantadine (administration & dosage), Amantadine (pharmacology), Animal, Animal model, Animals, Antiparkinson Agents (therapeutic use), Antiparkinson Agents (toxicity), Behavior, Animal (drug effects), Callithrix, Disease Models, Animal, Dopamine Agonists (administration & dosage), Dopamine Agonists (toxicity), Drug Synergism, Dyskinesia, Dyskinesia, Drug-Induced (diagnosis), Dyskinesia, Drug-Induced (drug therapy), Fructose (administration & dosage), Fructose (analogs & derivatives), Fructose (pharmacology), Levodopa (toxicity), MPTP Poisoning (drug therapy), MPTP‐lesioned primate, Male, Nervous system diseases, Neuroprotective Agents (therapeutic use), Parkinson Disease (drug therapy), Parkinson disease, Primates, Rat, Rats, Rats, Sprague-Dawley, Topiramate, amantadine, dyskinesia, topiramate.
- MESH :
- chemical , administration & dosage : Amantadine, Dopamine Agonists, Fructose.
- chemical , analogs & derivatives : Fructose.
- chemical , pharmacology : Amantadine, Fructose.
- chemical , therapeutic use : Antiparkinson Agents, Neuroprotective Agents.
- chemical , toxicity : Antiparkinson Agents, Dopamine Agonists, Levodopa.
- diagnosis : Dyskinesia, Drug-Induced.
- drug effects : Behavior, Animal.
- drug therapy : Dyskinesia, Drug-Induced, MPTP Poisoning, Parkinson Disease.
- Animals, Callithrix, Disease Models, Animal, Drug Synergism, Male, Rats, Rats, Sprague-Dawley.
Abstract
L‐Dopa‐induced dyskinesia in patients with Parkinson's disease can be alleviated by amantadine, an antagonist at N‐methyl‐D‐aspartate glutamate receptors. The antiepileptic drug topiramate, which blocks α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors, has also been shown to reduce dyskinesia. The purpose of this study was to examine the behavioral pharmacology of topiramate alone and in combination with amantadine in animal models of PD and L‐dopa‐induced dyskinesia. The effects of topiramate (5–20 mg/kg) and amantadine (5–20 mg/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and Rotarod performance were assessed alone and in combination in the 6‐hydroxydopamine‐lesioned rat following chronic L‐dopa treatment. Dyskinesia, parkinsonian disability, and “on‐time” were assessed in the MPTP‐lesioned nonhuman primate following administration of topiramate (5–20 mg/kg) and amantadine (0.1–1.0 mg/kg) alone and in combination. Topiramate and amantadine dose‐dependently reduced dyskinesia in the 6‐hydroxydopamine‐lesioned rat, whereas topiramate reduced Rotarod performance; there was no effect on parkinsonian disability in the MPTP‐lesioned nonhuman primate, in which both drugs reduced dyskinesia. Topiramate and amantadine exhibited differential antidyskinetic effects on dyskinesia elicited by the dopamine D1 receptor agonist SKF 38393 (2 mg/kg). Subthreshold doses of both drugs in combination had a synergistic effect on dyskinesia in the 6‐hydroxydopamine‐lesioned rat, with no worsening of motor performance; this effect was confirmed in the MPTP‐lesioned nonhuman primate, with a selective reduction in “bad on‐time.” These data confirm the antidyskinetic potential of topiramate and suggest that combination with low‐dose amantadine may allow better reduction of dyskinesia with no adverse motor effects. © 2011 Movement Disorder Society
Url:
DOI: 10.1002/mds.23867
Affiliations:
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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="2011-11">2011-11</date><biblScope unit="vol">26</biblScope><biblScope unit="issue">13</biblScope><biblScope unit="page" from="2354">2354</biblScope><biblScope unit="page" to="2363">2363</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">71D933598B65DAEC1D4FC362CD0E10BCCBB7BA8A</idno><idno type="DOI">10.1002/mds.23867</idno><idno type="ArticleID">MDS23867</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>6‐OHDA‐lesioned rat</term><term>Amantadine</term><term>Amantadine (administration & dosage)</term><term>Amantadine (pharmacology)</term><term>Animal</term><term>Animal model</term><term>Animals</term><term>Antiparkinson Agents (therapeutic use)</term><term>Antiparkinson Agents (toxicity)</term><term>Behavior, Animal (drug effects)</term><term>Callithrix</term><term>Disease Models, Animal</term><term>Dopamine Agonists (administration & dosage)</term><term>Dopamine Agonists (toxicity)</term><term>Drug Synergism</term><term>Dyskinesia</term><term>Dyskinesia, Drug-Induced (diagnosis)</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Fructose (administration & dosage)</term><term>Fructose (analogs & derivatives)</term><term>Fructose (pharmacology)</term><term>Levodopa (toxicity)</term><term>MPTP Poisoning (drug therapy)</term><term>MPTP‐lesioned primate</term><term>Male</term><term>Nervous system diseases</term><term>Neuroprotective Agents (therapeutic use)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson disease</term><term>Primates</term><term>Rat</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Topiramate</term><term>amantadine</term><term>dyskinesia</term><term>topiramate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Amantadine</term><term>Dopamine Agonists</term><term>Fructose</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Fructose</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amantadine</term><term>Fructose</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Antiparkinson Agents</term><term>Dopamine Agonists</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Behavior, Animal</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>MPTP Poisoning</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Callithrix</term><term>Disease Models, Animal</term><term>Drug Synergism</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Amantadine</term><term>Animal</term><term>Dyskinésie</term><term>Maladie de Parkinson</term><term>Modèle animal</term><term>Pathologie du système nerveux</term><term>Primates</term><term>Rat</term><term>Topiramate</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">L‐Dopa‐induced dyskinesia in patients with Parkinson's disease can be alleviated by amantadine, an antagonist at N‐methyl‐D‐aspartate glutamate receptors. The antiepileptic drug topiramate, which blocks α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors, has also been shown to reduce dyskinesia. The purpose of this study was to examine the behavioral pharmacology of topiramate alone and in combination with amantadine in animal models of PD and L‐dopa‐induced dyskinesia. The effects of topiramate (5–20 mg/kg) and amantadine (5–20 mg/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and Rotarod performance were assessed alone and in combination in the 6‐hydroxydopamine‐lesioned rat following chronic L‐dopa treatment. Dyskinesia, parkinsonian disability, and “on‐time” were assessed in the MPTP‐lesioned nonhuman primate following administration of topiramate (5–20 mg/kg) and amantadine (0.1–1.0 mg/kg) alone and in combination. Topiramate and amantadine dose‐dependently reduced dyskinesia in the 6‐hydroxydopamine‐lesioned rat, whereas topiramate reduced Rotarod performance; there was no effect on parkinsonian disability in the MPTP‐lesioned nonhuman primate, in which both drugs reduced dyskinesia. Topiramate and amantadine exhibited differential antidyskinetic effects on dyskinesia elicited by the dopamine D1 receptor agonist SKF 38393 (2 mg/kg). Subthreshold doses of both drugs in combination had a synergistic effect on dyskinesia in the 6‐hydroxydopamine‐lesioned rat, with no worsening of motor performance; this effect was confirmed in the MPTP‐lesioned nonhuman primate, with a selective reduction in “bad on‐time.” These data confirm the antidyskinetic potential of topiramate and suggest that combination with low‐dose amantadine may allow better reduction of dyskinesia with no adverse motor effects. © 2011 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Canada</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Manchester</li></region><settlement><li>Manchester</li></settlement><orgName><li>Université de Manchester</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Kobylecki, Christopher" sort="Kobylecki, Christopher" uniqKey="Kobylecki C" first="Christopher" last="Kobylecki">Christopher Kobylecki</name></region><name sortKey="Crossman, Alan R" sort="Crossman, Alan R" uniqKey="Crossman A" first="Alan R." last="Crossman">Alan R. Crossman</name><name sortKey="Kobylecki, Christopher" sort="Kobylecki, Christopher" uniqKey="Kobylecki C" first="Christopher" last="Kobylecki">Christopher Kobylecki</name><name sortKey="Kobylecki, Christopher" sort="Kobylecki, Christopher" uniqKey="Kobylecki C" first="Christopher" last="Kobylecki">Christopher Kobylecki</name><name sortKey="Ravenscroft, Paula" sort="Ravenscroft, Paula" uniqKey="Ravenscroft P" first="Paula" last="Ravenscroft">Paula Ravenscroft</name></country><country name="Canada"><noRegion><name sortKey="Hill, Michael P" sort="Hill, Michael P" uniqKey="Hill M" first="Michael P." last="Hill">Michael P. Hill</name></noRegion><name sortKey="Ravenscroft, Paula" sort="Ravenscroft, Paula" uniqKey="Ravenscroft P" first="Paula" last="Ravenscroft">Paula Ravenscroft</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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