ParkinsonCanadaV1, Main, Exploration, bibRecord, 003353

Apomorphine-induced changes in synaptic dopamine levels : Positron emission tomography evidence for presynaptic inhibition

Identifieur interne : 003353 ( Main/Exploration ); précédent : 003352; suivant : 003354

Apomorphine-induced changes in synaptic dopamine levels : Positron emission tomography evidence for presynaptic inhibition

Auteurs : Raul De La Fuente-Fernandez [Canada] ; Andrew S. Lim [Canada] ; Vesna Sossi [Canada] ; James E. Holden [États-Unis] ; Donald B. Calne [Canada] ; Thomas J. Ruth [Canada] ; A. Jon Stoessl [Canada]

Source :

Journal of cerebral blood flow and metabolism [ 0271-678X ] ; 2001.

RBID : Pascal:02-0039667

Descripteurs français

Pascal (Inist)
- Tomoscintigraphie, Positon, Parkinson maladie, Inhibition présynaptique, Dopamine, Raclopride, Technique, Exploration, Homme.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Antiparkinson Agents (therapeutic use), Apomorphine (pharmacology), Dopamine, Dopamine (metabolism), Emission tomography, Exploration, Female, Functional Laterality, Human, Humans, Male, Models, Biological, Parkinson Disease (diagnostic imaging), Parkinson Disease (drug therapy), Parkinson disease, Positron, Presynaptic Terminals (diagnostic imaging), Presynaptic inhibition, Raclopride, Raclopride (pharmacokinetics), Synapses (drug effects), Synapses (physiology), Technique, Tomography, Emission-Computed.
MESH :
- chemical , metabolism : Dopamine.
- chemical , pharmacokinetics : Raclopride.
- chemical , pharmacology : Apomorphine.
- chemical , therapeutic use : Antiparkinson Agents.
- diagnostic imaging : Parkinson Disease, Presynaptic Terminals.
- drug effects : Synapses.
- drug therapy : Parkinson Disease.
- physiology : Synapses.
- Female, Functional Laterality, Humans, Male, Models, Biological, Tomography, Emission-Computed.

Abstract

The authors developed a novel positron emission tomography method to estimate changes in the synaptic level of dopamine ([DA]) induced by direct dopamine agonists (for example, apomorphine) in patients with Parkinson disease, The method is based on the typical asymmetry of the nigrostriatal lesion that often occurs in Parkinson disease. Using the between-side difference (ipsilateral (I) and contralateral (C) putamen to the more affected body side) of the inverse of the putamen [¹¹C]raclopride binding potential (BP), the authors obtained 1/BP_I - 1/BP_C = K_D/B_maxK_DA([DA]_I - [DA]_C) at baseline (that is, before apomorphine administration) and 1/BP_I' - 1/BP_C'= K_D/B_maxK_DA([DA]_I' - [DA]_C') after apomorphine administration (assuming the concentration of apomorphine is equal in both putamina). The between-side difference in the estimated synaptic concentration of dopamine (diff[DA]) should remain constant unless apomorphine affects dopamine release differently between the two sides. The authors found that apomorphine given subcutaneously at doses of 0.03 and 0.06 mg/kg induced significant changes in their estimate of diff[DA] (P < 0.05). Such changes were more pronounced when only patients with a stable response to levodopa were considered (P < 0.01). These findings provide in vivo evidence that direct dopamine agonists can inhibit the release of endogenous dopamine. The authors propose that this effect is mainly mediated by the activation of presynaptic D₂/D₃ dopamine receptors.

Affiliations:

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiparkinson Agents (therapeutic use)</term>
<term>Apomorphine (pharmacology)</term>
<term>Dopamine</term>
<term>Dopamine (metabolism)</term>
<term>Emission tomography</term>
<term>Exploration</term>
<term>Female</term>
<term>Functional Laterality</term>
<term>Human</term>
<term>Humans</term>
<term>Male</term>
<term>Models, Biological</term>
<term>Parkinson Disease (diagnostic imaging)</term>
<term>Parkinson Disease (drug therapy)</term>
<term>Parkinson disease</term>
<term>Positron</term>
<term>Presynaptic Terminals (diagnostic imaging)</term>
<term>Presynaptic inhibition</term>
<term>Raclopride</term>
<term>Raclopride (pharmacokinetics)</term>
<term>Synapses (drug effects)</term>
<term>Synapses (physiology)</term>
<term>Technique</term>
<term>Tomography, Emission-Computed</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Raclopride</term>
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<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>Antiparkinson Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Parkinson Disease</term>
<term>Presynaptic Terminals</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Synapses</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Synapses</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Female</term>
<term>Functional Laterality</term>
<term>Humans</term>
<term>Male</term>
<term>Models, Biological</term>
<term>Tomography, Emission-Computed</term>
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<term>Positon</term>
<term>Parkinson maladie</term>
<term>Inhibition présynaptique</term>
<term>Dopamine</term>
<term>Raclopride</term>
<term>Technique</term>
<term>Exploration</term>
<term>Homme</term>
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<front><div type="abstract" xml:lang="en">The authors developed a novel positron emission tomography method to estimate changes in the synaptic level of dopamine ([DA]) induced by direct dopamine agonists (for example, apomorphine) in patients with Parkinson disease, The method is based on the typical asymmetry of the nigrostriatal lesion that often occurs in Parkinson disease. Using the between-side difference (ipsilateral (I) and contralateral (C) putamen to the more affected body side) of the inverse of the putamen [<sup>11</sup>
C]raclopride binding potential (BP), the authors obtained 1/BP<sub>I</sub>
 - 1/BP<sub>C</sub>
 = K<sub>D</sub>
/B<sub>max</sub>
K<sub>DA</sub>
([DA]<sub>I</sub>
 - [DA]<sub>C</sub>
) at baseline (that is, before apomorphine administration) and 1/BP<sub>I</sub>
' - 1/BP<sub>C</sub>
'= K<sub>D</sub>
/B<sub>max</sub>
K<sub>DA</sub>
([DA]<sub>I</sub>
' - [DA]<sub>C</sub>
') after apomorphine administration (assuming the concentration of apomorphine is equal in both putamina). The between-side difference in the estimated synaptic concentration of dopamine (diff[DA]) should remain constant unless apomorphine affects dopamine release differently between the two sides. The authors found that apomorphine given subcutaneously at doses of 0.03 and 0.06 mg/kg induced significant changes in their estimate of diff[DA] (P < 0.05). Such changes were more pronounced when only patients with a stable response to levodopa were considered (P < 0.01). These findings provide in vivo evidence that direct dopamine agonists can inhibit the release of endogenous dopamine. The authors propose that this effect is mainly mediated by the activation of presynaptic D<sub>2</sub>
/D<sub>3</sub>
 dopamine receptors.</div>
</front>
</TEI>
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<name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. Calne</name>
<name sortKey="Lim, Andrew S" sort="Lim, Andrew S" uniqKey="Lim A" first="Andrew S." last="Lim">Andrew S. Lim</name>
<name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name>
<name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name>
<name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name>
</country>
<country name="États-Unis"><region name="Wisconsin"><name sortKey="Holden, James E" sort="Holden, James E" uniqKey="Holden J" first="James E." last="Holden">James E. Holden</name>
</region>
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</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

Apomorphine-induced changes in synaptic dopamine levels : Positron emission tomography evidence for presynaptic inhibition

Apomorphine-induced changes in synaptic dopamine levels : Positron emission tomography evidence for presynaptic inhibition

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.