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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Rat Ultrasonic Vocalizations and Behavioral Neuropharmacology: From the Screening of Drugs to the Study of Disease
Current Neuropharmacology A Longitudinal FDG-PET Study of Transgenic Mice Overexpressing GSK- 3β in the Brain
Current Alzheimer Research Pramipexole Tachyphylaxis and its Management in Bipolar Depression
Letters in Drug Design & Discovery Expressed Emotion and Eating Disorders: An Updated Review
Current Psychiatry Reviews Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors
Current Neuropharmacology Meet Our Regional Editor:
Current Drug Discovery Technologies Targeting Striatal Metabotropic Glutamate Receptor Type 5 in Parkinson’s Disease: Bridging Molecular Studies and Clinical Trials
CNS & Neurological Disorders - Drug Targets History Repeats Itself: Pharmacodynamic Trends in the Treatment of Anxiety Disorders
Current Pharmaceutical Design Functional Characterisation of Homomeric Ionotropic Glutamate Receptors GluR1-GluR6 in a Fluorescence-Based High Throughput Screening Assay
Combinatorial Chemistry & High Throughput Screening Ethnobotanical Treatment Strategies Against Alzheimers Disease
Current Alzheimer Research Epilepsy and Neurosurgery: Historical Highlights
Current Pharmaceutical Design Neurological Disorders in Mice Lacking Glycogenes that are Mainly Expressed in Brain
CNS & Neurological Disorders - Drug Targets The Use of Microarrays to Study Childhood Developmental Brain Disorders
Current Genomics Homocysteine and Cerebral Stroke in Developing Countries
Current Medicinal Chemistry Immunomodulatory Effects of Medicinal Plants used for Vitiligo in Traditional Persian Medicine
Current Drug Discovery Technologies Highlights on Important Medicinal Plants for the Menopause Syndrome
Current Women`s Health Reviews Current Surgical Options for Patients with Epilepsy
Current Pharmaceutical Design Modulation of GABAA Receptors in the Treatment of Epilepsy
Current Pharmaceutical Design Non-Pharmacological Treatments for ADHD in Youth
Adolescent Psychiatry Neuroprotective Methodologies in the Treatment of Multiple Sclerosis Current Status of Clinical and Pre-clinical Findings
Current Drug Discovery Technologies