A comparative evaluation of the dopamine D(2/3) agonist radiotracer [11C](-)-N-propyl-norapomorphine and antagonist [11C]raclopride to measure amphetamine-induced dopamine release in the human striatum.
J Pharmacol Exp Ther
; 333(2): 533-9, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20103586
ABSTRACT
(-)-N-Propyl-norapomorphine (NPA) is a full dopamine D(2/3) receptor agonist, and [(11)C]NPA is a suitable radiotracer to image D(2/3) receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study, the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic dopamine was assessed with PET in healthy humans and compared with that of the reference D(2/3) receptor antagonist radiotracer [11C]raclopride. Ten subjects (eight females and two males) were studied on two separate days, a minimum of 1 week apart, both with [11C]raclopride and [11C]NPA at baseline and after the administration of 0.5 mg x kg(-1) oral d-amphetamine. Kinetic modeling with an arterial input function was used to derive the binding potential relative to nonspecific uptake (BPND) in the ventral striatum (VST), caudate (CAD), and putamen (PUT). [11C]Raclopride BPND was significantly reduced by 9.7 +/- 4.4, 8.4 +/- 4.2, and 14.7 +/- 4.8% after amphetamine administration in the VST, CAD, and PUT. [11C]NPA BPND was also reduced significantly, by 16.0 +/- 7.0, 16.1 +/- 6.1, and 21.9 +/- 4.9% after the same dose of amphetamine in the VST, CAD, and PUT. Although these results suggest that [11C]NPA is more vulnerable to endogenous competition by dopamine compared with [11C]raclopride by a factor of 1.49 to 1.90, the same data for a related outcome measure, binding potential relative to plasma concentration, was not significant. Nevertheless, these data add to the growing literature that suggests D(2/3) agonist radiotracers are more vulnerable to endogenous competition by dopamine than existing D(2/3) antagonist radiotracers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apomorfina
/
Dopamina
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Antagonistas de Dopamina
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Agonistas de Dopamina
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Corpo Estriado
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Racloprida
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Anfetamina
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos