Effects of Dopamine D2 Receptor Partial Agonist Antipsychotic Aripiprazole on Dopamine Synthesis in Human Brain Measured by PET with L-[β-11C]DOPA

Abstract

Dopamine D2 receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D2 receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [11C]raclopride and L-[β-11C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D2 receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D2 receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

Influence of O-Methylated Metabolite Penetrating the Blood–Brain Barrier to Estimation of Dopamine Synthesis Capacity in Human L-[β-11C]DOPA PET

“…Because of the simple and non-invasive procedure after omission of blood sampling, Gjedde-Patlak analysis with reference input function has been widely utilized to investigate the presynaptic function of dopamine neurons, including pathophysiological and clinical studies in patients with various neurologic diseases 1,4,5,9,10,18,20,[40][41][42] and in pharmacological studies. 9,19 We believe that our study provides a further advance for the use of L-[b-…”

Antidepressant response to aripiprazole augmentation associated with enhanced FDOPA utilization in striatum: A preliminary PET study

“…Thus, non-human primate studies with 11 C-DOPA PET revealed an inverse relationship between tracer utilization in striatum at baseline, and the decline evoked by challenge with aripiprazole (Ito et al, 2012), suggesting that net agonism at autoreceptors (thus decreasing utilization of exogenous DOPA tracers) was most pronounced in individuals with low basal activation of autoreceptors. Those authors interpreted their findings to support an action of aripiprazole as a stabilizer of dopamine synthesis , with efficacy depending upon individual factors.…”

When to start aripiprazole therapy in patients with bipolar mania

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