Abstract
A widely prescribed and potent short-acting hypnotic, zolpidem has become the mainstay for the treatment of middle-of-the-night sleeplessness. It is expected to be antagonized by caffeine. Paradoxically, in some cases caffeine appears to slightly enhance zolpidem sedation. The pharmacokinetic and pharmacodynamic nature of this odd effect remains unexplored. The purpose of this study is to reproduce a hypothetical molecular network recruited by caffeine when coadministered with zolpidem using Ingenuity Pathway Analysis. Thus generated, network drew attention to several possible contributors to caffeine sedation, such as tachykinin precursor 1, cannabinoid, and GABA receptors. The present overview is centered on the possibility that caffeine potentiation of zolpidem sedation does not involve a centralized interaction of specific neurotransmitters, but rather is contributed by its antioxidant capacity. It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem. This side effect of caffeine encourages further studies of multiple antioxidants as an attractive way to potentially increasing somnolence.
Keywords: Antioxidants, oxidative stress, sleep disorders, melatonin, GABAAβ3 receptor, networks, polypharmacology
Current Drug Targets
Title: The Paradox of Caffeine-Zolpidem Interaction: A Network Analysis
Volume: 10 Issue: 10
Author(s): Michael Myslobodsky
Affiliation:
Keywords: Antioxidants, oxidative stress, sleep disorders, melatonin, GABAAβ3 receptor, networks, polypharmacology
Abstract: A widely prescribed and potent short-acting hypnotic, zolpidem has become the mainstay for the treatment of middle-of-the-night sleeplessness. It is expected to be antagonized by caffeine. Paradoxically, in some cases caffeine appears to slightly enhance zolpidem sedation. The pharmacokinetic and pharmacodynamic nature of this odd effect remains unexplored. The purpose of this study is to reproduce a hypothetical molecular network recruited by caffeine when coadministered with zolpidem using Ingenuity Pathway Analysis. Thus generated, network drew attention to several possible contributors to caffeine sedation, such as tachykinin precursor 1, cannabinoid, and GABA receptors. The present overview is centered on the possibility that caffeine potentiation of zolpidem sedation does not involve a centralized interaction of specific neurotransmitters, but rather is contributed by its antioxidant capacity. It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem. This side effect of caffeine encourages further studies of multiple antioxidants as an attractive way to potentially increasing somnolence.
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Cite this article as:
Myslobodsky Michael, The Paradox of Caffeine-Zolpidem Interaction: A Network Analysis, Current Drug Targets 2009; 10 (10) . https://dx.doi.org/10.2174/138945009789577927
DOI https://dx.doi.org/10.2174/138945009789577927 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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