Evidence map›Paper›PMID 36565852›Full record

ReviewNeuropharmacology2023

Ketamine preservative benzethonium chloride potentiates hippocampal synaptic transmission and binds neurotransmitter receptors and transporters.

Kyle A Brown, Panos Zanos, Chris F Powels, Connor J Fix, Michael Michaelides, Edna F R Pereira, Ruin Moaddel, Todd D Gould

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

Review in Neuropharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  2. Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  3. Article
  4. Disassociating drug active ingredients from inactive: ketamine-like synaptic effects of a ketamine excipient.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    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

8 authors at 3 institutions in 1 country.

Kyle A BrownDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Panos ZanosDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Chris F PowelsDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Connor J FixBiomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224, USA.
Michael MichaelidesBiobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA; Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Edna F R PereiraDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Epidemiology and Public Health, Division of Translational Toxicology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Ruin MoaddelBiomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224, USA.
Todd D GouldDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Veterans Affairs Maryland Health Care System, Baltimore, MD, 21201, USA. Electronic address: gouldlab@me.com.
University of Maryland, Baltimore · USNational Institute on Aging · USNational Institute on Drug Abuse · US

Funding

Disease Status Drug Metabolism and New Drug Discovery ZIAAG000297 · NIA · NATIONAL INSTITUTE ON AGING · PI EGAN, JOSEPHINE · 2009 to 2025
$38.2M
Biobehavioral Imaging and Molecular Neuropsychopharmacology of Substance Abuse MechanismsZIADA000069 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI MICHAELIDES, MICHAEL · 2016 to 2025
$18.9M
Therapeutic Efficacy of Ketamine Metabolites for Depression TreatmentR01MH107615 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI GOULD, TODD D · 2016 to 2025
$7.2M
Mechanisms of sustained anti-neuroinflammatory actions of (2R, 6R)-hydroxynorketamine (HNK)R21AI145211 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI CLARK, SARAH MICHELLE, GOULD, TODD D · 2020 to 2021
$425k
Targeting the inflammatory response to treat post-traumatic anxiety and depression.I01BX003631 · VA · BALTIMORE VA MEDICAL CENTER · PI GOULD, TODD D · 2017 to 2021
–
Hydroxynorketamine for the Treatment of PTSD and AnhedoniaI01BX004062 · VA · BALTIMORE VA MEDICAL CENTER · PI GOULD, TODD D · 2019 to 2023
–
BLRD VA I01 BX003631BLRD VA I01 BX004062Intramural NIH HHS ZIA DA000069NIAID NIH HHS R21 AI145211NIDA NIH HHS HHSN271201800023CNIMH NIH HHS R01 MH107615
6 · The paper itself

Abstract

Benzethonium chloride (BZT) is an excipient used in numerous products including (R,S)-ketamine (ketamine) drug formulations for human and veterinary use. Emerging evidence indicates BZT is pharmacologically active. BZT may therefore contribute to some of the clinical or preclinical effects observed with ketamine. In the present study, we evaluated: (i) the affinity of BZT for neurotransmitter receptors and transporters, (ii) the effects of BZT on hippocampal synaptic transmission in vitro, and (iii) plasma and brain concentrations of BZT following its intraperitoneal administration to male CD1 mice. Radioligand binding assays determined the affinity of BZT for neurotransmitter targets. Effects of BZT on field excitatory postsynaptic potentials (fEPSPs) were established via electrophysiological recordings from slices collected from male C57BL/6J mice. The binding assays revealed that BZT binds to numerous receptors (e.g., σ

Indexed as

KetamineAnimalsBenzethoniumHippocampusHumansMaleMiceMice, Inbred C57BLReceptors, NeurotransmitterSynaptic TransmissionBenzethoniumKetamineReceptors, NeurotransmitterBenzethoniumElectrophysiologyExcipientHippocampusKetamineSynaptic transmission

Identifiers

PMID36565852
PMCPMC9867909
OpenAlexW4313214811

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.