Chronopharmacological strategies focused on chrono-drug discovery

Publication date: Available online 5 June 2019Source: Pharmacology & TherapeuticsAuthor(s): Shigehiro Ohdo, Satoru Koyanagi, Naoya MatsunagaAbstractIn mammals, the circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN) and influences a multitude of biological processes, including the sleep–wake rhythm. Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbation of these rhythms is associated with pathogenic conditions such as cancer, metabolic syndrome, cardiovascular disease, sleep disorder and depression. Clock genes ultimately control a vast array of circadian rhythms involved in physiology and behavior. They regulate several diseases described above. Chronotherapy is especially relevant when the risk and/or intensity of symptoms of a disease vary predictably over time. The effectiveness and toxicity of several drugs vary depending on the dosing time. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics but also the pharmacokinetics of a medication. The underlying mechanisms are associated with the 24-h rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Identifying a rhythmic marker based on the molecular clock for choosing dosing time can lead to the progress and diffusion of chronopharmacotherapy. To monitor the rhythmic markers such as clock genes, it might be useful to choose the mos...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research