Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia.
Identifieur interne : 000060 ( France/Analysis ); précédent : 000059; suivant : 000061Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia.
Auteurs : Erwan Bezard [France] ; Elisabetta Tronci ; Elsa Y. Pioli ; Qin Li ; Gregory Porras ; Anders Björklund ; Manolo CartaSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2013.
English descriptors
- KwdEn :
- Amantadine (therapeutic use), Amphetamine (diagnostic use), Animals, Apomorphine (pharmacology), Disease Models, Animal, Dopamine Agents (adverse effects), Dyskinesia, Drug-Induced (drug therapy), Dyskinesia, Drug-Induced (etiology), Female, Levodopa (adverse effects), Macaca fascicularis, Medial Forebrain Bundle (physiology), Motor Activity (drug effects), Oxidopamine (toxicity), Parkinson Disease (drug therapy), Parkinson Disease (etiology), Parkinsonian Disorders (drug therapy), Piperazines (therapeutic use), Psychomotor Performance (drug effects), Rats, Rats, Sprague-Dawley, Serotonin Receptor Agonists (therapeutic use), Time Factors, Tyrosine 3-Monooxygenase (metabolism).
- MESH :
- chemical , adverse effects : Dopamine Agents, Levodopa.
- chemical , diagnostic use : Amphetamine.
- chemical , metabolism : Tyrosine 3-Monooxygenase.
- chemical , pharmacology : Apomorphine.
- chemical , therapeutic use : Amantadine, Piperazines, Serotonin Receptor Agonists.
- drug effects : Motor Activity, Psychomotor Performance.
- drug therapy : Dyskinesia, Drug-Induced, Parkinson Disease, Parkinsonian Disorders.
- etiology : Dyskinesia, Drug-Induced, Parkinson Disease.
- physiology : Medial Forebrain Bundle.
- chemical , toxicity : Oxidopamine.
- Animals, Disease Models, Animal, Female, Macaca fascicularis, Rats, Rats, Sprague-Dawley, Time Factors.
Abstract
The serotonin (5-hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l-3,4-dihydroxyphenylalanine (levodopa [l-dopa])-induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5-HT 1A/1B receptor agonist eltoprazine to counteract l-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned rats and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l-dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine-induced worsening of l-dopa therapeutic effects.
DOI: 10.1002/mds.25366
PubMed: 23389842
Affiliations:
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pubmed:23389842Le document en format XML
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Pioli</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name></author><author><name sortKey="Bjorklund, Anders" sort="Bjorklund, Anders" uniqKey="Bjorklund A" first="Anders" last="Björklund">Anders Björklund</name></author><author><name sortKey="Carta, Manolo" sort="Carta, Manolo" uniqKey="Carta M" first="Manolo" last="Carta">Manolo Carta</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amantadine (therapeutic use)</term><term>Amphetamine (diagnostic use)</term><term>Animals</term><term>Apomorphine (pharmacology)</term><term>Disease Models, Animal</term><term>Dopamine Agents (adverse effects)</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Female</term><term>Levodopa (adverse effects)</term><term>Macaca fascicularis</term><term>Medial Forebrain Bundle (physiology)</term><term>Motor Activity (drug effects)</term><term>Oxidopamine (toxicity)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (etiology)</term><term>Parkinsonian Disorders (drug therapy)</term><term>Piperazines (therapeutic use)</term><term>Psychomotor Performance (drug effects)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Serotonin Receptor Agonists (therapeutic use)</term><term>Time Factors</term><term>Tyrosine 3-Monooxygenase (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Dopamine Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Amphetamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Apomorphine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Amantadine</term><term>Piperazines</term><term>Serotonin Receptor Agonists</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Activity</term><term>Psychomotor Performance</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Medial Forebrain Bundle</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Oxidopamine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Macaca fascicularis</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The serotonin (5-hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l-3,4-dihydroxyphenylalanine (levodopa [l-dopa])-induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5-HT 1A/1B receptor agonist eltoprazine to counteract l-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned rats and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l-dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine-induced worsening of l-dopa therapeutic effects.</div></front></TEI><affiliations><list><country><li>France</li></country><settlement><li>Bordeaux</li></settlement></list><tree><noCountry><name sortKey="Bjorklund, Anders" sort="Bjorklund, Anders" uniqKey="Bjorklund A" first="Anders" last="Björklund">Anders Björklund</name><name sortKey="Carta, Manolo" sort="Carta, Manolo" uniqKey="Carta M" first="Manolo" last="Carta">Manolo Carta</name><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name><name sortKey="Pioli, Elsa Y" sort="Pioli, Elsa Y" uniqKey="Pioli E" first="Elsa Y" last="Pioli">Elsa Y. Pioli</name><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name><name sortKey="Tronci, Elisabetta" sort="Tronci, Elisabetta" uniqKey="Tronci E" first="Elisabetta" last="Tronci">Elisabetta Tronci</name></noCountry><country name="France"><noRegion><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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