Article date: May 2019
By: Anne C. Baakman, Rob Zuiker, Joop M.A. Gerven, Nicholas Gross, Ronghua Yang, Michael Fetell, Ari Gershon, Yossi Gilgun‐Sherki, Edward Hellriegel, Ofer Spiegelstein in Volume 85, Issue 5, pages 970-985
Aims
In previous studies, the histamine‐3 receptor antagonist CEP‐26401 had a subtle effect on spatial working memory, with the best effect seen at the lowest dose tested (20 μg), and a dose‐dependent disruption of sleep. In the current study, 3 low‐dose levels of CEP‐26401 were compared with modafinil and donepezil.
Methods
In this double‐blind, placebo‐ and positive‐controlled, randomized, partial 6‐way cross‐over study, 40 healthy subjects received single doses of placebo, CEP‐26401 (5, 25 or 125 μg) or modafinil 200 mg or donepezil 10 mg. Pharmacokinetic and pharmacodynamic measurements were performed predose and at designated time points postdose.
Results
The main endpoint between‐errors of the spatial working memory‐10‐boxes task only improved for the 125 μg dose of CEP‐26401 with a difference of 2.92 (confidence interval [CI] –1.21 to 7.05), 3.24 (CI –1.57 to 8.04) and 7.45 (CI 2.72 to 12.19) for respectively the 5, 25 and 125 μg dose of CEP‐26401, −1.65 (CI –0.572 to 1.96) for modafinil and − 3.55 (CI –7.13 to 0.03) for donepezil. CEP‐26401 induced an improvement of adaptive tracking, saccadic peak velocity and reaction time during N‐back, but a dose‐related inhibition of sleep and slight worsening of several cognitive parameters at the highest dose. CEP‐26401 significantly changed several subjective visual analogue scales, which was strongest at 25 μg, causing the same energizing and happy feeling as modafinil, but with a more relaxed undertone.
Discussion
Of the doses tested, the 25 μg dose of CEP‐26401 had the most optimal balance between favourable subjective effects and sleep inhibition. Whether CEP‐26401 can have beneficial effects in clinical practice remains to be studied.
DOI: 10.1111/bcp.13885
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