Evidence map›Paper›PMID 40590485›Full record

ArticleBehavioural pharmacology2025

Procognitive effects of methyl 2-amino-3-methoxybenzoate (or daopine) may involve the dorsal striatal anthranilic acid pathway and mutimetabolite-multitarget pharmacology.

Yami Bright, Helene I V Amatdjais-Groenen, Michel M M Verheij, Petra H H van den Broek, Marcia Spoelder, Dorien Maas, Rick Greupink, Gerard J M Martens, Judith R Homberg

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In one paragraph

Article in Behavioural pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Yami BrightDepartment of Cognitive Neuroscience, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour.
Helene I V Amatdjais-GroenenInstitute for Molecules and Materials, System Chemistry, Radboud University.
Michel M M VerheijDepartment of Cognitive Neuroscience, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour.
Petra H H van den BroekDepartment of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences.
Marcia SpoelderDepartment of Cognitive Neuroscience, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour.
Dorien MaasDepartment of Cognitive Neuroscience, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour.
Rick GreupinkDepartment of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences.
Gerard J M MartensDepartment of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Faculty of Science, Nijmegen, The Netherlands.
Judith R HombergDepartment of Cognitive Neuroscience, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour.

Funding

None
6 · The paper itself

Abstract

Multifunctional drug treatment is currently the most promising approach in neuropsychopharmacology to overcome complex disorders, such as schizophrenia. We previously showed that the natural protoalkaloid, methyl 2-amino-3-methoxybenzoate [or daopine (DAO)] has procognitive effects in animal models of schizophrenia. Because DAO is a metabolite of the anthranilic acid biosynthesis pathway in Nigella damascena plant seeds, we sought to find out if DAO exerts its procognitive effects via the 'anthranilic acid-brain-pathway-twin' and mutimetabolite-multitarget pharmacology. We explored the procognitive effects of DAO using the operant set shift task in a rat model of attentional flexibility deficits induced by L-kynurenine, the precursor of both kynurenic acid and anthranilic acid. HPLC and liquid chromatography-mass spectrometry was used to identify brain and plasma DAO metabolites and the effects of DAO on dorsal striatal anthranilic acid. DAO attenuated kynurenine-induced cognitive deficits. We identified for the first time the brain (DAO-1 and DAO-3) and plasma (DAO-1 and DAO-2) metabolites of DAO, which remarkably are all methylated derivatives of 3-hydroxyanthranilic acid (3-OHAA), an endogenous brain astrocytic metabolite of anthranilic acid playing a crucial role in cognition. In vitro , DAO-2 and DAO-3 significantly reduced oxidative activity, lipid peroxidation, inflammation, and amyloid β-42-aggregation, all of which represent processes that play an important protective role against cognitive dysfunction. The results strengthen our hypothesis that administering small molecules structurally related to anthranilic acid/3-OHAA, such as DAO, may provide a multitarget strategy for the prevention and treatment of cognitive deficits in schizophrenia, and more broadly, in other cognitive disorders, such as Alzheimer's disease.

Indexed as

Nootropic Agentsortho-AminobenzoatesAnimalsBrainCognitionCorpus StriatumDisease Models, AnimalKynurenic AcidKynurenineMaleRatsRats, Sprague-DawleySchizophreniaanthranilic acidKynurenic AcidKynureninemethyl anthranilateNootropic Agentsortho-Aminobenzoatesanthranilic acid pathwaycognitive disorderdaopinedopaminemultitargetschizophreniaWistar rat

Identifiers

PMID40590485
PMCPMC12329809

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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.