Evidence map›Paper›PMID 32474681›Full record

ArticlePsychopharmacology2020

Novel, non-nitrocatechol catechol-O-methyltransferase inhibitors modulate dopamine neurotransmission in the frontal cortex and improve cognitive flexibility.

Spencer Byers, Ingrid P Buchler, Michael DePasquale, Helen L Rowley, Rajiv S Kulkarni, Lucy Pinder, Anna Kolobova, Cailian Li, Vinh Au, Daniel Akuma and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Cortical dopamine reduces the impact of motivational biases governing automated behaviour.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
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  4. Article
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  10. Inhibition of Catechol-Frontiers in behavioral neuroscience · 2020
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Spencer ByersLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Ingrid P BuchlerLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Michael DePasqualeLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Helen L RowleyRenaSci Limited, Nottingham, UK.
Rajiv S KulkarniRenaSci Limited, Nottingham, UK.
Lucy PinderRenaSci Limited, Nottingham, UK.
Anna KolobovaLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Cailian LiLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Vinh AuLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Daniel AkumaLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Gongliang ZhangLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Huijun WeiLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Sharon C CheethamRenaSci Limited, Nottingham, UK.
James C BarrowLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Gregory V CarrLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA. greg.carr@libd.org.ORCID http://orcid.org/0000-0002-6091-6729
Johns Hopkins University · USRenaSci (United Kingdom) · GB

Funding

Drug discovery of COMT inhibitors to treat cognitive deficits in schizophreniaR01MH107126 · NIMH · LIEBER INSTITUTE, INC. · PI BARROW, JAMES · 2015 to 2019
$4.1M
NIMH NIH HHS R01 MH107126NIMH NIH HHS R01MH107126
6 · The paper itself

Abstract

rationaleCognitive impairment is a primary feature of many neuropsychiatric disorders and there is a need for new therapeutic options. Catechol-O-methyltransferase (COMT) inhibitors modulate cortical dopaminergic function and have been proposed as potential cognitive enhancers. Unfortunately, currently available COMT inhibitors are not good candidates due to either poor blood-brain barrier penetration or severe toxicity.

objectivesTo address the need for safe, brain-penetrant COMT inhibitors, we tested multiple novel compounds in a set of preclinical in vivo efficacy assays in rats to determine their ability to inhibit COMT function and viability as potential clinical candidates.

methodsWe measured the change in concentration of dopamine (DA) metabolites in cerebrospinal fluid (CSF) from the cisterna magna and extracellular fluid (ECF) from the frontal cortex produced by our novel compounds. Additionally, we tested the effects of our brain-penetrant COMT inhibitors in an attentional set-shifting assay (ASST). We benchmarked the performance of the novel COMT inhibitors to the effects produced by the known COMT inhibitor tolcapone.

resultsWe found that multiple COMT inhibitors, exemplified by LIBD-1 and LIBD-3, significantly modulated dopaminergic function measured as decreases in homovanillic acid (HVA) and increases in 3,4-Dihydroxyphenylacetic acid (DOPAC), two DA metabolites, in CSF and the frontal cortex. Additionally, we found that LIBD-1 significantly improved cognitive flexibility in the ASST, an effect previously reported following tolcapone administration.

conclusionsThese results demonstrate that LIBD-1 is a novel COMT inhibitor with promising in vivo activity and the potential to serve as a new therapy for cognitive impairment.

Indexed as

3,4-Dihydroxyphenylacetic AcidAnimalsCatechol O-MethyltransferaseCatechol O-Methyltransferase InhibitorsCognitionDopamineFemaleFrontal LobeHomovanillic AcidMaleMicrodialysisRatsRats, Sprague-DawleySynaptic Transmission3,4-Dihydroxyphenylacetic AcidCatechol O-MethyltransferaseCatechol O-Methyltransferase InhibitorsDopamineHomovanillic AcidCatechol-O-methyltransferaseCognitive impairmentCortexDopamineExecutive functionMicrodialysisParkinson’s diseaseRatSchizophreniaTolcapone

Identifiers

PMID32474681
PMCPMC7790123
OpenAlexW3032263508

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.