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In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propyl-norapomorphine ([11C]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride.
- Source :
-
Synapse (New York, N.Y.) [Synapse] 2004 Jun 01; Vol. 52 (3), pp. 188-208. - Publication Year :
- 2004
-
Abstract
- (-)-N-Propyl-norapomorphine (NPA) is a full dopamine (DA) D2 receptor agonist and [11C]NPA is a suitable radiotracer to image D2 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 DA was assessed with PET in baboons and compared to that of the reference D2 receptor antagonist radiotracer [11C]raclopride. Three male baboons were studied with [11C]raclopride and [11C]NPA under baseline conditions and following administration of the potent DA releaser amphetamine (0.3, 0.5, and 1.0 mg kg(-1) i.v.). Kinetic modeling with an arterial input function was used to derive the striatal specific-to-nonspecific equilibrium partition coefficient (V3"). [11C]Raclopride V3" was reduced by 24 +/- 10%, 32 +/- 6%, and 44 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. [11C]NPA V3" was reduced by 32 +/- 2%, 45 +/- 3%, and 53 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. Thus, endogenous DA was more effective at competing with [11C]NPA binding compared to [11C]raclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, [11C]NPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease.<br /> (Copyright 2004 Wiley-Liss, Inc.)
- Subjects :
- Algorithms
Amphetamine blood
Amphetamine pharmacokinetics
Amphetamine pharmacology
Animals
Binding, Competitive drug effects
Dopamine Uptake Inhibitors blood
Dopamine Uptake Inhibitors pharmacokinetics
Dopamine Uptake Inhibitors pharmacology
Dose-Response Relationship, Drug
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Papio
Tomography, Emission-Computed
Apomorphine analogs & derivatives
Dopamine metabolism
Dopamine Agonists pharmacology
Dopamine Antagonists chemical synthesis
Dopamine Antagonists pharmacokinetics
Raclopride chemical synthesis
Raclopride pharmacokinetics
Radiopharmaceuticals chemical synthesis
Radiopharmaceuticals pharmacokinetics
Receptors, Dopamine D2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0887-4476
- Volume :
- 52
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Synapse (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 15065219
- Full Text :
- https://doi.org/10.1002/syn.20013