Evidence map›Paper›PMID 33609599›Full record

ArticlePharmacology, biochemistry, and behavior2021

N-Substituted-3-alkoxy-derivatives of dextromethorphan are functional NMDA receptor antagonists in vivo: Evidence from an NMDA-induced seizure model in rats.

Jeffrey M Witkin, Rok Cerne, Amy H Newman, Sari Izenwasser, Jodi L Smith, Frank C Tortella

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

Article in Pharmacology, biochemistry, and behavior, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Sigma-1 receptor and seizures.Pharmacological research · 2023
    Review
  3. Article
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

6 authors at 6 institutions in 2 countries.

Jeffrey M WitkinLaboratory of Antiepileptic Drug Discovery, Ascension St. Vincent, Indianapolis, IN, USA; Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI, USA. Electronic address: witkinconsult@gmail.com.
Rok CerneLaboratory of Antiepileptic Drug Discovery, Ascension St. Vincent, Indianapolis, IN, USA; Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Amy H NewmanMolecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Sari IzenwasserDepartment of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Jodi L SmithLaboratory of Antiepileptic Drug Discovery, Ascension St. Vincent, Indianapolis, IN, USA.
Frank C TortellaDepartment of Neuropharmacology and Molecular Biology, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
National Institutes of Health · USSt. Vincent Hospital · USUniversity of Ljubljana · SIUniversity of Miami · USUniversity of Wisconsin–Milwaukee · USWalter Reed Army Institute of Research · US

Funding

Novel Probes for the Monoamine TransportersZIADA000389 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI NEWMAN, AMY HAUCK · 2009 to 2025
$14.4M
Design of New Therapeutic Agents to Treat SchizophreniaR01MH096463 · NIMH · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2013 to 2017
$1.9M
Synthesis of Alpha2/Alpha3 GABA Agonists to Treat Neuropathic PainR01NS076517 · NINDS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2012 to 2015
$1.3M
Intramural NIH HHS ZIA DA000389NIMH NIH HHS R01 MH096463NINDS NIH HHS R01 NS076517
6 · The paper itself

Abstract

Interest in developing NMDA receptor antagonists with reduced side-effects for neurological and psychiatric disorders has been re-energized by the recent introduction of esketamine into clinical practice for treatment-resistant depression. Structural analogs of dextromethorphan bind with low affinity to the NMDA receptor ion channel, have functional effects in vivo, and generally display a lower propensity for side-effects than that of ketamine and other higher affinity antagonists. As such, the aim of the present study was to determine whether a series of N-substituted-3-alkoxy-substituted dextromethorphan analogs produce their anticonvulsant effects through NMDA receptor blockade. Compounds were studied against NMDA-induced seizures in rats. Compounds were administered intracerebroventricularly in order to mitigate confounds of drug metabolism that arise from systemic administration. Comparison of the anticonvulsant potencies to their affinities for NMDA, σ1, and σ2 binding sites were made in order to evaluate the contribution of these receptors to anticonvulsant efficacy. The potencies to block convulsions were positively associated with their affinities to bind to the NMDA receptor ion channel ([

Indexed as

AlcoholsAnimalsAnticonvulsantsBinding SitesDextromethorphanDextrorphanDisease Models, AnimalExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsInfusions, IntraventricularLigandsMaleN-MethylaspartateRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateAlcoholsalkoxyl radicalAnticonvulsantsDextromethorphanDextrorphanExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsLigandsN-MethylaspartateReceptors, N-Methyl-D-AspartateReceptors, sigmaSigma-1 ReceptorDextromethorphan analogsNMDA receptorsNMDA seizuresSigma receptors

Identifiers

PMID33609599
PMCPMC9659398
OpenAlexW3130291264

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.