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• W2074117907 abstract "In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [(11)C](+)-PHNO ([(11)C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [(3)H]raclopride, which binds to both affinity states.We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [(11)C](+)-PHNO and [(3)H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for (11)C and (3)H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure.In response to D2 antagonists, partial agonist or full agonist, [(11)C](+)-PHNO and [(3)H]raclopride SBRs responded indistinguishably in terms of both ED(50) and Hill slope (e.g., (-)-NPA ED(50) values are 0.027 and 0.023 mg/kg for [(11)C](+)-PHNO and [(3)H]raclopride, respectively). In response to AMPH challenge, [(11)C](+)-PHNO and [(3)H]raclopride SBRs were inhibited to the same degree.We have shown that the SBRs of [(11)C](+)-PHNO- and [(3)H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments." @default.
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• W2074117907 date "2008-01-01" @default.
• W2074117907 modified "2023-09-23" @default.
• W2074117907 title "Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo" @default.
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• W2074117907 doi "https://doi.org/10.1016/j.nucmedbio.2007.08.005" @default.
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