Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates

Brown, Roger M.; Crane, Alison M.; Goldman, Patricia S.

doi:10.1016/0006-8993(79)90132-x

Cited by 311 publications

(150 citation statements)

References 71 publications

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“…A possible explanation for these regionally varying dose occupancy curves might be the following: D 2 receptor occupancies observed under antipsychotics with moderate or low affinity might be influenced by endogenous dopamine (Seeman, 2002). Dopamine concentrations in animal striatum are significantly higher compared to cortical concentrations when measured with tissue homogenate or microdialysis techniques (Brown et al, 1979;Pehek, 1999). Furthermore, there are markedly different kinetics of dopamine release and reuptake across brain regions (Garris and Wightman, 1994).…”

Section: Discussionmentioning

confidence: 99%

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Gründer

Landvogt²,

Vernaleken

et al. 2005

Neuropsychopharmacol

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Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D 2 /D 3 dopamine receptors in human striatum. Here, the occupancy of D 2 /D 3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [ 18 F]fallypride PET scan. Receptor occupancy was calculated as percent reduction in binding potential relative to unblocked values measured in seven normal volunteers. Mean D 2 /D 3 receptor occupancy was statistically significantly higher in cortical (inferior temporal cortex 55%) than in striatal regions (putamen 36%, caudate 43%, po0.005). While the maximum attainable receptor occupancy E max approached 100% both in the striatum and cortex, the plasma concentration at 50% of E max (ED 50 ) was much higher in the putamen (950 ng/ml) than in the inferior temporal cortex (333 ng/ml). Clozapine binds preferentially to cortical D 2 /D 3 receptors over a wide range of plasma concentrations. This selectivity is lost at extremely high plasma levels. Occupancy of cortical receptors approaches 60% with plasma clozapine in the range 350-400 ng/ml, which corresponds to the threshold for antipsychotic efficacy of clozapine. Extrastriatal binding of clozapine may be more relevant to its antipsychotic actions than striatal. However, further studies with an intraindividual comparison of untreated vs treated state are desirable to confirm this finding.

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Section: Discussionmentioning

confidence: 99%

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Gründer

Landvogt²,

Vernaleken

et al. 2005

Neuropsychopharmacol

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“…Further, there is some evidence that schizophrenic patients may have reduced density of frontal D1 receptors (Okubo et al 1997). DA innervation in the frontal cortex is greatest in the precentral gyrus (Brown et al 1979), the location of the frontal eye fields (Paus 1996) a structure important for smooth pursuit (MacAvoy et al 1991, O'Driscoll et al 1999b) and antisaccades (Guitton et al 1985;O'Driscoll et al 1995) as well as for attention (Kodaka et al 1997). Reduced activity in the frontal eye fields (measured by regional cerebral blood flow) has been linked to abnormal pursuit in schizophrenia (Ross et al 1995;O'Driscoll et al 1999b).…”

Section: Discussionmentioning

confidence: 99%

Nicotine and Behavioral Markers of Risk for Schizophrenia A Double-Blind, Placebo-Controlled, Cross-Over Study

Dépatie

2002

Neuropsychopharmacology

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140

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“…Plotting C i (t)/C i Ј(t) versus ͵ 0 t C i Ј͑͒d/C i Ј͑t͒, after time t* yields a straight line with the slope k i and intercept F. In the present study, the occipital cortex was used as a reference region with no irreversible binding, because this region is known to have the lowest dopamine concentration (Brown et al, 1979) and lowest aromatic L-amino acid decarboxylase activity (Lloyd and Hornykiewicz, 1972). The range of equilibrium time t* of 29 -89 min was used (Ito et al, 2006(Ito et al, , 2007.…”

Section: Methodsmentioning

confidence: 99%

Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-¹¹C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?

Ito¹,

Takano²,

Takahashi³

et al. 2009

J. Neurosci.

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receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis capacity by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D 2 receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis capacity. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

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Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates

Cited by 311 publications

References 71 publications

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Nicotine and Behavioral Markers of Risk for Schizophrenia A Double-Blind, Placebo-Controlled, Cross-Over Study

Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-¹¹C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?

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Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates

Cited by 311 publications

References 71 publications

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Nicotine and Behavioral Markers of Risk for Schizophrenia A Double-Blind, Placebo-Controlled, Cross-Over Study

Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-11C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?

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Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-¹¹C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?