Sleep Pharmacogenetics: Personalized Sleep-Wake Therapy
| Autor: | Hans-Peter Landolt, Amandine Valomon, Sebastian C. Holst |
|---|---|
| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2016 |
| Předmět: |
Sleep Wake Disorders
0301 basic medicine 10050 Institute of Pharmacology and Toxicology 610 Medicine & health Pharmacology Biology Toxicology Bioinformatics Non-rapid eye movement sleep Melatonin 03 medical and health sciences 0302 clinical medicine Neurochemical medicine Animals Humans Neurochemistry Neurotransmitter Agents business.industry Neuropeptides Brain 3005 Toxicology 3004 Pharmacology 030104 developmental biology Pharmacogenetics 10076 Center for Integrative Human Physiology Pharmacogenomics 570 Life sciences biology Personalized medicine Sleep business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Annual Review of Pharmacology and Toxicology. 56:577-603 |
| ISSN: | 1545-4304 0362-1642 |
| DOI: | 10.1146/annurev-pharmtox-010715-103801 |
| Popis: | Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players in the regulation and maintenance of sleep-wake-dependent changes in neuronal activity and the sleep-wake continuum. Dysregulation of these neurochemical systems leads to sleep-wake disorders. Most currently available pharmacological treatments are symptomatic rather than causal, and their beneficial and adverse effects are often variable and in part genetically determined. To evaluate opportunities for evidence-based personalized medicine with present and future sleep-wake therapeutics, we review here the impact of known genetic variants affecting exposure of and sensitivity to drugs targeting the neurochemistry of sleep-wake regulation and the pathophysiology of sleep-wake disturbances. Many functional polymorphisms modify drug response phenotypes relevant for sleep. To corroborate the importance of these and newly identified variants for personalized sleep-wake therapy, human sleep pharmacogenetics should be complemented with pharmacogenomic investigations, research about sleep-wake-dependent pharmacological actions, and studies in mice lacking specific genes. These strategies, together with future knowledge about epigenetic mechanisms affecting sleep-wake physiology and treatment outcomes, may lead to potent and safe novel therapies for the increasing number of sleep-disordered patients (e.g., in aged populations). |
| Databáze: | OpenAIRE |
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