In vivo Binding Behavior of Dopamine Receptor Agonist (+)−PD 128907 and Implications for the “Ceiling Effect” in Endogenous Competition Studies with [11C]Raclopride—a Positron Emission Tomography Study in Macaca mulatta

Open Access
Publisher Website
Google Scholar
Abstract
In in vivo positron emission tomography (PET) studies, dopamine that is released secondary to amphetamine administration appears unable to achieve a receptor occupancy that is significantly higher than 50% (“ceiling effect”). Also with exogenous agonists no studies have reported a higher than 50% occupancy. To investigate the feasibility of exceeding 50% occupancy in vivo with a dopamine receptor agonist we administered D2/D3 agonist (+)−PD 128907 over an extensive dose range. Two anesthetised Macaca mulatta males were used in a bolus-infusion protocol for [11C]raclopride. (+)- PD 128907 was administered as an intravenous challenge during separate PET scans in a dose range of 10 to 10000 nmol/kg. Occupancy by (+)−PD 128907 was estimated by comparing the binding before and after challenge. In a striatal region of interest, receptor occupancy by (+)−PD 128907 increased in an orderly dose-dependent manner to a maximum of at least 85%. This is the first indication that virtually all dopamine D2/D3 receptors in the striatum are in principle accessible to agonist binding. In the case of dopamine a number of protective mechanisms may be responsible for the ceiling effect.

This publication has 13 references indexed in Scilit: