Evidence map›Paper›PMID 31693759›Full record

ReviewJournal of neurochemistry2020

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence.

Trevor W Stone

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of neurochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

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  20. Kynurenines and Mitochondrial Disturbances in Multiple Sclerosis.International journal of molecular sciences · 2025
    Review

17 more citing papers are in PubMed but not listed here.

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

1 author at 1 institution in 1 country.

Trevor W StoneInstitute for Neuroscience and Psychology, University of Glasgow, Glasgow, G12 8QQ, UK.ORCID 0000-0002-5532-0031
University of Glasgow · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As a major metabolite of kynurenine in the oxidative metabolism of tryptophan, kynurenic acid is of considerable biological and clinical importance as an endogenous antagonist of glutamate in the central nervous system. It is most active as an antagonist at receptors sensitive to N-methyl-D-aspartate (NMDA) which regulate neuronal excitability and plasticity, brain development and behaviour. It is also thought to play a causative role in hypo-glutamatergic conditions such as schizophrenia, and a protective role in several neurodegenerative disorders, notably Huntington's disease. An additional hypothesis, that kynurenic acid could block nicotinic receptors for acetylcholine in the central nervous system has been proposed as an alternative mechanism of action of kynurenate. However, the evidence for this alternative mechanism is highly controversial, partly because at least eight earlier studies concluded that kynurenic acid blocked NMDA receptors but not nicotinic receptors and five subsequent, independent studies designed to repeat the results have failed to do so. Many studies considered to support the alternative 'nicotinic' hypothesis have been based on the use of analogs of kynurenate such as 7-chloro-kynurenic acid, or putatively nicotinic modulators such as galantamine, but a detailed analysis of the pharmacology of these compounds suggests that the results have often been misinterpreted, especially since the pharmacology of galantamine itself has been disputed. This review examines the evidence in detail, with the conclusion that there is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors. Therefore, since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, with some activity at GPR35 sites and Aryl Hydrocarbon Receptors, results with kynurenic acid should be interpreted only in terms of these confirmed sites of action.

Indexed as

AnimalsBinding SitesBrainBrain ChemistryGalantamineHumansKynurenic AcidNicotinic AntagonistsReceptors, Aryl HydrocarbonReceptors, G-Protein-CoupledReceptors, NicotinicReceptors, N-Methyl-D-AspartateReproducibility of ResultsGalantamineGPR35 protein, humanKynurenic AcidNicotinic AntagonistsReceptors, Aryl HydrocarbonReceptors, G-Protein-CoupledReceptors, NicotinicReceptors, N-Methyl-D-Aspartatecholinergic receptorsgalantaminekynurenic acidkynureninenicotinic receptorsNMDA receptors

Identifiers

PMID31693759
PMCPMC7078985
OpenAlexW2988690127

What OpenQuestion holds

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LicenceCC BY
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.