Effects of amisulpride on human resting cerebral perfusion

Viviani, Roberto; Graf, Heiko; Wiegers, Maike; Abler, Birgit

doi:10.1007/s00213-013-3091-z

Cited by 20 publications

(24 citation statements)

References 63 publications

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“…Indeed, Franklin et al [] posit that changes in blood flow induced by pharmacological agents may be “masquerading as volumetric changes.” Their study reported changes in CBF, measured using arterial spin labeling (ASL), overlapping with same‐direction changes in GM volume from standard T1‐weighted images following acute administration of the GABA agonist, baclofen. This notion is particularly relevant in the context of volumetric changes induced by acute antipsychotic administration, as rapid alterations in blood flow produced by single doses of these drugs have consistently been reported [Fernández‐Seara et al, ; Handley et al, ; Mehta et al, ; Viviani et al, ]. Resolving this issue requires the assessment of the acute effect of antipsychotics on both regional blood flow and structural MR metrics in a placebo controlled setting [Hoflich et al, ].…”

Section: Introductionmentioning

confidence: 99%

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers

Hawkins

Wood

Vernon

et al. 2017

Human Brain Mapping

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Chronic administration of antipsychotic drugs has been linked to structural brain changes observed in patients with schizophrenia. Recent MRI studies have shown rapid changes in regional brain volume following just a single dose of these drugs. However, it is not clear if these changes represent real volume changes or are artefacts ("apparent" volume changes) due to drug-induced physiological changes, such as increased cerebral blood flow (CBF). To address this, we examined the effects of a single, clinical dose of three commonly prescribed antipsychotics on quantitative measures of T1 and regional blood flow of the healthy human brain. Males (n 5 42) were randomly assigned to one of two parallel groups in a double-blind, placebo-controlled, randomized, three-period cross-over study Additional Supporting Information may be found in the online version of this article. design. One group received a single oral dose of either 0.5 or 2 mg of risperidone or placebo during each visit. The other received olanzapine (7.5 mg), haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1-weighted images were acquired at the estimated peak plasma concentration of the drug. All three drugs caused localized increases in striatal blood flow, although drug and region specific effects were also apparent. In contrast, all assessments of T1 and brain volume remained stable across sessions, even in those areas experiencing large changes in CBF. This illustrates that a single clinically relevant oral dose of an antipsychotic has no detectable acute effect on T1 in healthy volunteers. We further provide a methodology for applying quantitative imaging methods to assess the acute effects of other compounds on structural MRI metrics. Hum Brain Mapp 39:319-331, 2018.V C 2017 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers

Hawkins

Wood

Vernon

et al. 2017

Human Brain Mapping

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“…We would expect such vascular effects of dopaminergic modulation to be rather homogeneously distributed, reflecting a direct vasodilatory effect on cerebral blood vessels, as observed for levodopa (Leenders et al, 1985) or DA per se (Sabatini et al, 1991; Krimer et al, 1998). One previous ASL study showed decrements in CBF in the prefrontal cortex (PFC) after 7-day treatment with amisulpride, an antagonist at D2/D3 receptors (Viviani et al, 2013). The acute application of amphetamines, however, which block the reuptake and thereby increase the levels of DA, lowers CBF in the nigrostriatal but not in the cortical system (Lavyne et al, 1977).…”

Section: Introductionmentioning

confidence: 99%

Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults

Michels

Scherpiet

Staempfli³

et al. 2016

IJNPPY

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Background:The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known.Methods:In this randomized crossover, placebo-controlled, and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the nonergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow differences induced by the 3 substances.Results:We found that quetiapine reduced perfusion in the occipital (early visual areas) and bilateral cerebellar cortex relative to placebo. In contrast, quetiapine enhanced cerebral blood flow (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area, insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased cerebral blood flow compared with placebo in the caudate nucleus, putamen, middle frontal, supplementary motor area, and brainstem (substantia nigra), but reduced cerebral blood flow in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger cerebral blood flow relative to quetiapine in the hypothalamus, cerebellum, and substantia nigra.Conclusions:Our results indicate that quetiapine and pramipexole differentially modulate regional baseline cerebral blood flow. Both substances act on the dopaminergic system, although they affect distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected cerebral blood flow of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system.

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“…Studies of brain perfusion at rest have shown that psychoactive substances may affect the brain according to different regional patterns. Antipsychotics, for example, have been shown to increase of metabolism and perfusion in the basal ganglia, and at a variable degree to decrease them in the cortex, especially in the frontal lobes . Likewise, comparative studies of brain perfusion at rest of antidepressants with different profiles show different perfusion patterns dependent on drug‐target profile (Fig.…”

Section: Expression Of Dmes In the Brainmentioning

confidence: 99%

Polymorphism in CYP2D6 and CYP2C19, members of the cytochrome P450 mixed‐function oxidase system, in the metabolism of psychotropic drugs

Stingl

Viviani

2015

J Intern Med

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Abstract. Stingl J, Viviani R (University of Bonn Medical Faculty, Bonn; University of Ulm, Ulm; Germany). Polymorphism in CYP2D6 and CYP2C19, members of the cytochrome P450 mixed-function oxidase system, in the metabolism of psychotropic drugs (Review). J Intern Med 2015; 277: 167-177.Numerous studies in the field of psychopharmacological treatment have investigated the possible contribution of genetic variability between individuals to differences in drug efficacy and safety, motivated by the wide individual variation in treatment response. Genomewide analyses have been conducted in several large-scale studies on antidepressant drug response. However, no consistent findings have emerged from these studies. In a recent meta-analysis of genomewide data from the three studies capturing common variation for association with symptomatic improvement and remission revealed the absence of any strong genetic association and failed to replicate results of individual studies in the pooled data. However, there are good reasons to consider the possible importance of pharmacogenetic variants separately. These variants explain a large portion of the manifold variability in individual drug metabolism. More than 20 psychotropic drugs have now been relabelled by the FDA adding information on polymorphic drug metabolism and therapeutic recommendations. Furthermore, dose recommendations for polymorphisms in drug metabolizing enzymes, first and foremost CYP2D6 and CYP2C19, have been issued with the advice to reduce the dosage in poor metabolizers to 50% or less (in eight cases), or to choose an alternative treatment. Beside the well-described role in hepatic drug metabolism, these enzymes are also expressed in the brain and play a role in biotransformation of endogenous substrates. These polymorphisms may therefore modulate brain metabolism and affect the function of the neural substrates of cognition and emotion.

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Effects of amisulpride on human resting cerebral perfusion

Cited by 20 publications

References 63 publications

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers

Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults

Polymorphism in CYP2D6 and CYP2C19, members of the cytochrome P450 mixed‐function oxidase system, in the metabolism of psychotropic drugs

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