Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Hot Topics
  • Published:

Disassociating drug active ingredients from inactive: ketamine-like synaptic effects of a ketamine excipient

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout


  1. Pottel J, Armstrong D, Zou L, Fekete A, Huang X-P, Torosyan H, et al. The activities of drug inactive ingredients on biological targets. Science 2020;369:403–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dai Q, Liu X, He T, Yang C, Jiang J, Fang Y, et al. Excipient of paclitaxel induces metabolic dysregulation and unfolded protein response. Iscience. 2021;24:103170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Coates KM, Flood P. Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes. Br J Pharm. 2001;134:871–79.

    Article  CAS  Google Scholar 

  4. Durieux ME, Nietgen GW. Synergistic inhibition of muscarinic signaling by ketamine stereoisomers and the preservative benzethonium chloride. Anesthesiology 1997;86:1326–33.

    Article  CAS  PubMed  Google Scholar 

  5. Long Y, Lin Z, Xia M, Zheng W, Li Z. Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride. Toxicol Appl Pharm. 2013;267:155–66.

    Article  CAS  Google Scholar 

  6. Brown KA, Zanos P, Powels CF, Fix CJ, Michaelides M, Pereira EF, et al. Ketamine preservative benzethonium chloride potentiates hippocampal synaptic transmission and binds neurotransmitter receptors and transporters. Neuropharmacology. 2022;225:109403.

    Article  PubMed  Google Scholar 

Download references



This work was supported by NIH/NIMH R01MH107615 and U.S. Department of Veterans Affairs Merit Awards 1I01BX004062 and 1I01BX006018 to TDG. The binding and functional profile of BZT were performed by the National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP; University of North Carolina, Chapel Hill, NC; Contract # HHSN-271-2018-00023-C). The NIMH PDSP is directed by Bryan L. Roth at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Author information

Authors and Affiliations



KAB and TDG contributed to the conception of the work; KAB wrote the manuscript and TDG critically revised the work.

Corresponding author

Correspondence to Todd D. Gould.

Ethics declarations

Competing interests

TDG has received research funding from Allergan Pharmaceuticals during the preceding three years. TDG is listed as an inventor in patents and patent applications related to the pharmacology and use of a ketamine metabolite, (2R,6R)-hydroxynorketamine, in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. TDG has assigned his patent rights to the University of Maryland, Baltimore, but will share a percentage of any royalties that may be received by the University of Maryland, Baltimore. KAB declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brown, K.A., Gould, T.D. Disassociating drug active ingredients from inactive: ketamine-like synaptic effects of a ketamine excipient. Neuropsychopharmacol. 49, 301–302 (2024).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links