Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla.
Rationale: Lithium is an effective treatment for bipolar disorder, but safety issues complicate its clinical use. The antioxidant drug, ebselen, may be a possible lithium-mimetic based on its ability to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. Objectives: Ou...
| Publicado en: | Psychopharmacology Vol. 233; no. 6; pp. 1097 - 1105 |
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| Autores principales: | , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Mar2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=113139771&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 113139771 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Mar2016 vid: 233 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 113139771 10.1007/s00213-015-4189-2 113139771 ppf: 1097 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla. aug: au: Masaki, Charles Sharpley, Ann Godlewska, Beata Berrington, Adam Hashimoto, Tasuku Singh, Nisha Vasudevan, Sridhar Emir, Uzay Churchill, Grant Cowen, Philip affil: Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford OX3 7JX UK sug: ab: Rationale: Lithium is an effective treatment for bipolar disorder, but safety issues complicate its clinical use. The antioxidant drug, ebselen, may be a possible lithium-mimetic based on its ability to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. Objectives: Our primary aim was to determine whether ebselen lowered levels of inositol in the human brain. We also assessed the effect of ebselen on other brain neurometabolites, including glutathione, glutamate, glutamine, and glutamate + glutamine (Glx) Methods: Twenty healthy volunteers were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, random-order, crossover design. Two hours after the final dose of ebselen/placebo, participants underwent proton magnetic resonance spectroscopy (H MRS) at 7 tesla (T) with voxels placed in the anterior cingulate and occipital cortex. Neurometabolite levels were calculated using an unsuppressed water signal as a reference and corrected for individual cerebrospinal fluid content in the voxel. Results: Ebselen produced no effect on neurometabolite levels in the occipital cortex. In the anterior cingulate cortex, ebselen lowered concentrations of inositol ( p = 0.028, Cohen's d = 0.60) as well as those of glutathione ( p = 0.033, d = 0.58), glutamine ( p = 0.024, d = 0.62), glutamate ( p = 0.01, d = 0.73), and Glx ( p = 0.001, d = 1.0). Conclusions: The study suggests that ebselen produces a functional inhibition of IMPase in the human brain. The effect of ebselen to lower glutamate is consistent with its reported ability to inhibit the enzyme, glutaminase. Ebselen may have potential as a repurposed treatment for bipolar disorder. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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