Evidence map›Paper›PMID 42332075›Full record

ArticleNature structural & molecular biology2026

Structural basis of opioid receptor activation by PCP and ketamine.

Qianru Jiang, Jianming Han, Eve J Fine, Nokomis Ramos-Gonzalez, Vipin Ashok Rangari, Micaela V Ruiz, Madalyn L Critz, Carl-Mikael Suomivuori, Jing Wang, Talia L Albert and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2026. 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

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

1 citing paper in PubMed.

  1. Review
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

19 authors.

Qianru Jiang *Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.
Jianming Han *Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.
Eve J Fine *Department of Bioengineering, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7404-897X
Nokomis Ramos-GonzalezCenter for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID http://orcid.org/0000-0002-9398-8956
Vipin Ashok RangariCenter for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID http://orcid.org/0000-0002-9721-6195
Micaela V RuizDepartment of Pharmacology, UW Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
Madalyn L CritzDepartment of Pharmacology, UW Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
Carl-Mikael SuomivuoriDepartment of Computer Science, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-2445-8791
Jing WangDepartment of Pharmacology and NIMH Psychoactive Drug Screening Program, UNC Chapel Hill Medical School, Chapel Hill, NC, USA.
Talia L AlbertDepartment of Pharmacology and NIMH Psychoactive Drug Screening Program, UNC Chapel Hill Medical School, Chapel Hill, NC, USA.
Kyle WhiddonDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Kunpeng LiDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Michael J RobertsonVerna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0003-2610-680X
Xi-Ping HuangDepartment of Pharmacology and NIMH Psychoactive Drug Screening Program, UNC Chapel Hill Medical School, Chapel Hill, NC, USA.
Benjamin B LandDepartment of Pharmacology, UW Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.
Susruta MajumdarCenter for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID http://orcid.org/0000-0002-2931-3823
Jonathan F FayDepartment of Biochemistry and Molecular Biology, University of Maryland Baltimore, Baltimore, MD, USA. JFay@som.umaryland.edu.ORCID http://orcid.org/0000-0003-1822-2384
Ron O DrorDepartment of Computer Science, Stanford, CA, USA. ron.dror@stanford.edu.ORCID http://orcid.org/0000-0002-6418-2793
Tao CheCenter for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA. taoche@wustl.edu.ORCID http://orcid.org/0000-0002-1620-3027

Funding

Structural Determinants of Kappa Opioid Receptor SignalingR35GM143061 · NIGMS · WASHINGTON UNIVERSITY · PI Tao Che · 2021 to 2026
$2.1M
Mechanisms and Regulations of kappa Opioid Receptor SignalingR01DA058020 · NIDA · WASHINGTON UNIVERSITY · PI Tao Che · 2024 to 2026
$1.4M
Stanford Chem-H Chemistry/Biology Interface Predoctoral Training ProgramT32GM120007 · NIGMS · STANFORD UNIVERSITY · PI BERTOZZI, CAROLYN · 2016 to 2020
$1.2M
From protein structures to effective drugs via machine learning and molecular simulationR35GM158122 · NIGMS · STANFORD UNIVERSITY · PI Ron Dror · 2025 to 2026
$1.0M
NIDA NIH HHS R01 DA058020NIGMS NIH HHS R35 GM143061NIGMS NIH HHS R35 GM158122NIGMS NIH HHS T32 GM120007
6 · The paper itself

Abstract

Ketamine offers rapid relief for treatment-resistant depression and severe pain in the clinic, providing immediate benefits that traditional medications often fail to deliver. While its antagonistic action at the N-methyl-D-aspartate receptor (NMDAR) is a key mechanism, ketamine's dual nature as both a promising treatment and a drug with abuse potential suggests its therapeutic effects extend beyond NMDAR inhibition. Here we provide structural evidence of human opioid receptors bound to ketamine and its parent analog phencyclidine (PCP), supporting that both ligands can directly bind and activate opioid receptors. The structures, together with site-directed mutagenesis and structure-activity relationship studies, identify key motifs involved in ketamine and PCP recognition and efficacy modulation. Furthermore, we determine the structure of the ligand-free state of human κ opioid receptor, revealing molecular details before ligand engagement. Compared to PCP, ketamine displays more notable binding dynamics in the orthosteric site that may contribute to its unique pharmacology at opioid receptors. Our findings highlight the importance of including opioid receptors to fully understand ketamine's versatility in clinical settings.

Indexed as

KetaminePhencyclidineReceptors, OpioidReceptors, Opioid, kappaBinding SitesHumansLigandsModels, MolecularMutagenesis, Site-DirectedProtein BindingStructure-Activity RelationshipKetamineLigandsPhencyclidineReceptors, OpioidReceptors, Opioid, kappa

Identifiers

PMID42332075
PMCPMC13392676

What OpenQuestion holds

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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.