ParkinsonFranceV1, Main, Exploration, bibRecordById, pubmed:10360765

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's Disease

Identifieur interne : 003F34 ( Main/Exploration ); précédent : 003F33; suivant : 003F35

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's Disease

Auteurs : O. Rascol [France] ; O. Blin [France] ; C. Thalamas [France] ; S. Descombes [France] ; C. Soubrouillard [France] ; P. Azulay [France] ; N. Fabre [France] ; F. Viallet [France] ; K. Lafnitzegger [États-Unis] ; S. Wright [États-Unis] ; J. H. Carter [États-Unis] ; J. G. Nutt [États-Unis]

Source :

Annals of neurology [ 0364-5134 ] ; 1999.

RBID : Pascal:99-0342238

Descripteurs français

Pascal (Inist)
- Parkinson maladie, Agoniste, Récepteur dopaminergique D1, Etude préalable, Traitement, Homme, Chimiothérapie, Antiparkinsonien, Promédicament, ABT-431.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Aged, Agonist, Antiparkinson agent, Chemotherapy, D1 Dopamine receptor, Double-Blind Method, Female, Human, Humans, Male, Middle Aged, Parkinson Disease (drug therapy), Parkinson disease, Previous study, Prodrug, Prodrugs (adverse effects), Prodrugs (pharmacology), Prodrugs (therapeutic use), Pyridines (adverse effects), Pyridines (pharmacology), Pyridines (therapeutic use), Tetrahydronaphthalenes (adverse effects), Tetrahydronaphthalenes (pharmacology), Tetrahydronaphthalenes (therapeutic use), Treatment.
MESH :
- chemical , adverse effects : Prodrugs, Pyridines, Tetrahydronaphthalenes.
- drug therapy : Parkinson Disease.
- chemical , pharmacology : Prodrugs, Pyridines, Tetrahydronaphthalenes.
- chemical , therapeutic use : Prodrugs, Pyridines, Tetrahydronaphthalenes.
- Aged, Double-Blind Method, Female, Humans, Male, Middle Aged.

Abstract

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.

Affiliations:

Le document en format XML

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<term>Agonist</term>
<term>Antiparkinson agent</term>
<term>Chemotherapy</term>
<term>D1 Dopamine receptor</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Human</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinson Disease (drug therapy)</term>
<term>Parkinson disease</term>
<term>Previous study</term>
<term>Prodrug</term>
<term>Prodrugs (adverse effects)</term>
<term>Prodrugs (pharmacology)</term>
<term>Prodrugs (therapeutic use)</term>
<term>Pyridines (adverse effects)</term>
<term>Pyridines (pharmacology)</term>
<term>Pyridines (therapeutic use)</term>
<term>Tetrahydronaphthalenes (adverse effects)</term>
<term>Tetrahydronaphthalenes (pharmacology)</term>
<term>Tetrahydronaphthalenes (therapeutic use)</term>
<term>Treatment</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Prodrugs</term>
<term>Pyridines</term>
<term>Tetrahydronaphthalenes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Prodrugs</term>
<term>Pyridines</term>
<term>Tetrahydronaphthalenes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Prodrugs</term>
<term>Pyridines</term>
<term>Tetrahydronaphthalenes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Parkinson maladie</term>
<term>Agoniste</term>
<term>Récepteur dopaminergique D1</term>
<term>Etude préalable</term>
<term>Traitement</term>
<term>Homme</term>
<term>Chimiothérapie</term>
<term>Antiparkinsonien</term>
<term>Promédicament</term>
<term>ABT-431</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>États-Unis</li>
</country>
<region><li>Illinois</li>
<li>Midi-Pyrénées</li>
<li>Occitanie (région administrative)</li>
<li>Oregon</li>
<li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement><li>Aix-en-Provence</li>
<li>Marseille</li>
<li>Toulouse</li>
</settlement>
</list>
<tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Rascol, O" sort="Rascol, O" uniqKey="Rascol O" first="O." last="Rascol">O. Rascol</name>
</region>
<name sortKey="Azulay, P" sort="Azulay, P" uniqKey="Azulay P" first="P." last="Azulay">P. Azulay</name>
<name sortKey="Blin, O" sort="Blin, O" uniqKey="Blin O" first="O." last="Blin">O. Blin</name>
<name sortKey="Descombes, S" sort="Descombes, S" uniqKey="Descombes S" first="S." last="Descombes">S. Descombes</name>
<name sortKey="Fabre, N" sort="Fabre, N" uniqKey="Fabre N" first="N." last="Fabre">N. Fabre</name>
<name sortKey="Soubrouillard, C" sort="Soubrouillard, C" uniqKey="Soubrouillard C" first="C." last="Soubrouillard">C. Soubrouillard</name>
<name sortKey="Thalamas, C" sort="Thalamas, C" uniqKey="Thalamas C" first="C." last="Thalamas">C. Thalamas</name>
<name sortKey="Viallet, F" sort="Viallet, F" uniqKey="Viallet F" first="F." last="Viallet">F. Viallet</name>
</country>
<country name="États-Unis"><region name="Illinois"><name sortKey="Lafnitzegger, K" sort="Lafnitzegger, K" uniqKey="Lafnitzegger K" first="K." last="Lafnitzegger">K. Lafnitzegger</name>
</region>
<name sortKey="Carter, J H" sort="Carter, J H" uniqKey="Carter J" first="J. H." last="Carter">J. H. Carter</name>
<name sortKey="Nutt, J G" sort="Nutt, J G" uniqKey="Nutt J" first="J. G." last="Nutt">J. G. Nutt</name>
<name sortKey="Wright, S" sort="Wright, S" uniqKey="Wright S" first="S." last="Wright">S. Wright</name>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson en France (serveur d'exploration)

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's Disease

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's Disease

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	La maladie de Parkinson en France (serveur d'exploration)
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