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01-06-2015 | Research Article

Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy

Authors: Nisha K. Ramakrishnan, Marianne Schepers, Gert Luurtsema, Csaba J. Nyakas, Philip H. Elsinga, Kiichi Ishiwata, Rudi A. J. O. Dierckx, Aren van Waarde

Published in: Molecular Imaging and Biology | Issue 3/2015

Abstract

Purpose

Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model.

Procedures

Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([¹¹C]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [¹¹C]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.

Results

Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition.

Conclusion

The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.

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Title: Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy
Authors: Nisha K. Ramakrishnan
Marianne Schepers
Gert Luurtsema
Csaba J. Nyakas
Philip H. Elsinga
Kiichi Ishiwata
Rudi A. J. O. Dierckx
Aren van Waarde
Publication date: 01-06-2015
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 3/2015
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-014-0808-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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