An appraisal of the antiparkinsonian activity of piribedil in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐treated common marmosets
Identifieur interne : 005710 ( Main/Exploration ); précédent : 005709; suivant : 005711An appraisal of the antiparkinsonian activity of piribedil in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐treated common marmosets
Auteurs : Lance Smith [Royaume-Uni] ; Maria De Salvia [Royaume-Uni] ; Jenner [Royaume-Uni] ; C. David Marsden [Royaume-Uni]Source :
- Movement Disorders [ 0885-3185 ] ; 1996-03.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Singe.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, Administration, Oral, Agonist, Animal, Animal model, Animals, Antiemetics (pharmacology), Antiparkinson Agents (administration & dosage), Antiparkinson Agents (toxicity), Antiparkinson agent, Behavioural deficits, Callithrix, Chemotherapy, Common marmosets, Domperidone (pharmacology), Dopamine receptor, Dose-Response Relationship, Drug, Drug Synergism, Female, Locomotion (drug effects), Locomotor activity, Male, Monkey, Motor Skills (drug effects), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (drug therapy), Parkinson disease, Parkinson's disease, Piribedil, Piribedil (administration & dosage), Piribedil (toxicity), Premedication, Receptors, Dopamine D2 (drug effects), Stereotyped Behavior (drug effects), Treatment.
- MESH :
- chemical , administration & dosage : Antiparkinson Agents, Piribedil.
- chemical , drug effects : Receptors, Dopamine D2.
- chemical , pharmacology : Antiemetics, Domperidone.
- chemical , toxicity : Antiparkinson Agents, Piribedil.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Locomotion, Motor Skills, Stereotyped Behavior.
- drug therapy : Parkinson Disease, Secondary.
- Administration, Oral, Animals, Callithrix, Dose-Response Relationship, Drug, Drug Synergism, Female, Male, Premedication.
Abstract
The D2 dopamine agonist piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP)–treated primates to reevaluate the antiparkinsonian ability of piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by brady kinesia and other motor deficits. Oral administration of a solution of piribedil [1–(3,4–methylenedioxybenzyl)–4–(2–pyrimidinyl) piperazine] produced a dose–related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of piribedil did not induce nausea or retching in MPTP‐treated marmosets. In these animals, piribedil caused a more marked and and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of piribedil alone. In addition, piribedil induced increased vigilance and awareness. These data show that piribedil can reverse akinesia and rigidity in MPTP‐treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjuction with domperidone. These data indicate that piribedil should be an effective monotherapy for Parkinson's disease.
Url:
DOI: 10.1002/mds.870110203
Affiliations:
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Le document en format XML
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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="1996-03">1996-03</date><biblScope unit="vol">11</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="125">125</biblScope><biblScope unit="page" to="135">135</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">3A8D5EC6C2F8DD45D6D5B30A233600CFF5E52960</idno><idno type="DOI">10.1002/mds.870110203</idno><idno type="ArticleID">MDS870110203</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine</term><term>Administration, Oral</term><term>Agonist</term><term>Animal</term><term>Animal model</term><term>Animals</term><term>Antiemetics (pharmacology)</term><term>Antiparkinson Agents (administration & dosage)</term><term>Antiparkinson Agents (toxicity)</term><term>Antiparkinson agent</term><term>Behavioural deficits</term><term>Callithrix</term><term>Chemotherapy</term><term>Common marmosets</term><term>Domperidone (pharmacology)</term><term>Dopamine receptor</term><term>Dose-Response Relationship, Drug</term><term>Drug Synergism</term><term>Female</term><term>Locomotion (drug effects)</term><term>Locomotor activity</term><term>Male</term><term>Monkey</term><term>Motor Skills (drug effects)</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (drug therapy)</term><term>Parkinson disease</term><term>Parkinson's disease</term><term>Piribedil</term><term>Piribedil (administration & dosage)</term><term>Piribedil (toxicity)</term><term>Premedication</term><term>Receptors, Dopamine D2 (drug effects)</term><term>Stereotyped Behavior (drug effects)</term><term>Treatment</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiparkinson Agents</term><term>Piribedil</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Dopamine D2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiemetics</term><term>Domperidone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Antiparkinson Agents</term><term>Piribedil</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Locomotion</term><term>Motor Skills</term><term>Stereotyped Behavior</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term><term>Animals</term><term>Callithrix</term><term>Dose-Response Relationship, Drug</term><term>Drug Synergism</term><term>Female</term><term>Male</term><term>Premedication</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Agoniste</term><term>Animal</term><term>Antiparkinsonien</term><term>Chimiothérapie</term><term>Modèle animal</term><term>Parkinson maladie</term><term>Piribédil</term><term>Récepteur dopaminergique</term><term>Singe</term><term>Traitement</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Singe</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The D2 dopamine agonist piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP)–treated primates to reevaluate the antiparkinsonian ability of piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by brady kinesia and other motor deficits. Oral administration of a solution of piribedil [1–(3,4–methylenedioxybenzyl)–4–(2–pyrimidinyl) piperazine] produced a dose–related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of piribedil did not induce nausea or retching in MPTP‐treated marmosets. In these animals, piribedil caused a more marked and and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of piribedil alone. In addition, piribedil induced increased vigilance and awareness. These data show that piribedil can reverse akinesia and rigidity in MPTP‐treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjuction with domperidone. These data indicate that piribedil should be an effective monotherapy for Parkinson's disease.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li></region></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Smith, Lance" sort="Smith, Lance" uniqKey="Smith L" first="Lance" last="Smith">Lance Smith</name></region><name sortKey="De Salvia, Maria" sort="De Salvia, Maria" uniqKey="De Salvia M" first="Maria" last="De Salvia">Maria De Salvia</name><name sortKey="Jenner" sort="Jenner" uniqKey="Jenner" last="Jenner">Jenner</name><name sortKey="Marsden, C David" sort="Marsden, C David" uniqKey="Marsden C" first="C. David" last="Marsden">C. David Marsden</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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