Circadian Rhythms: Mechanisms and Therapeutic Implications
Open accessAbstract
The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cues in the synchronization of many, if not most, peripheral clocks, suggesting that the temporal coordination of metabolism and proliferation is a major task of the mammalian timing system. The inactivation of noxious food components by hepatic, intestinal, and renal detoxification systems is among the metabolic processes regulated in a circadian manner, with the understanding of the involved clock output pathways emerging. The rhythmic control of xenobiotic detoxification provides the molecular basis for the dosing time-dependence of drug toxicities and efficacy. This knowledge can in turn be used in improving or designing chronotherapeutics for the patients who suffer from many of the major human diseases.
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Pharmacokinetics are driven by the absorption, distribution, metabolism, and excretion of a medication, each of which may be modulated by circadian rhythms.
“Furthermore, pharmacokinetics are driven by the absorption, distribution, metabolism, and excretion of a medication, each of which may be modulated by circadian rhythms (172).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [172]
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Cellular Circadian Pacemaking and the Role of Cytosolic Rhythms
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- Authors
- Levi, F., & Schibler, U.
- Affiliations
- INSERM U776, Unité de Chronothérapie, Service de Cancérologie, Hôpital Paul Brousse et Université Paris XI, 94800 Villejuif, France;
- University of Geneva (CH)
- ORCID
- Schibler, Ueli
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2007-02-01
- Volume
- 47
- Issue
- 1
- Pages
- 593-628
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W2126157274
- Cited by
- 645
- References
- 156
- Citations by year
- 2026: 25 · 2025: 20 · 2024: 28 · 2023: 31 · 2022: 23 · 2021: 38 · 2020: 43 · 2019: 23 · 2018: 21 · 2017: 23 · 2016: 34 · 2015: 27 · 2014: 49 · 2013: 43 · 2012: 42
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian rhythm, suprachiasmatic nucleus, circadian clock, peripheral oscillators, rest-activity rhythm, xenobiotic detoxification, drug toxicity, timing of drug administration, chronotherapy, metabolism, proliferation
- MeSH terms
- Animals, Biological Clocks, Circadian Rhythm, Humans, Inactivation, Metabolic, Suprachiasmatic Nucleus, Drug Design, Xenobiotics, Drug Delivery Systems, Chronotherapy
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