Pharmacogenetics of Modafinil After Sleep Loss: Catechol-O-Methyltransferase Genotype Modulates Waking Functions But Not Recovery Sleep
| Autor: | H. H. Jung, S Xu, Hans-Peter Landolt, Sereina Bodenmann, Wolfgang Berger, Ulrich F O Luhmann, Michael Arand |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Genotype medicine.medical_treatment Modafinil Pharmacology Catechol O-Methyltransferase Young Adult 03 medical and health sciences 0302 clinical medicine Double-Blind Method mental disorders Humans Medicine Pharmacology (medical) Prospective Studies Effects of sleep deprivation on cognitive performance Benzhydryl Compounds Wakefulness Saliva 030304 developmental biology 0303 health sciences Cross-Over Studies Polymorphism Genetic Catechol-O-methyl transferase business.industry Dopaminergic Sleep in non-human animals Stimulant Sleep deprivation Pharmacogenetics Sleep Deprivation medicine.symptom Sleep business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Clinical Pharmacology & Therapeutics. 85:296-304 |
| ISSN: | 1532-6535 0009-9236 |
| Popis: | Sleep loss impairs waking functions and is homeostatically compensated in recovery sleep. The mechanisms underlying the consequences of prolonged wakefulness are unknown. The stimulant modafinil may promote primarily dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT) catalyzes the breakdown of cerebral dopamine. A functional Val158Met polymorphism reduces COMT activity, and Val/Val homozygous individuals presumably have lower dopaminergic signaling in the prefrontal cortex than do Met/Met homozygotes. We quantified the contribution of this polymorphism to the effects of sleep deprivation and modafinil on subjective state, cognitive performance, and recovery sleep in healthy volunteers. Two-time 100 mg modafinil potently improved vigor and well-being, and maintained baseline performance with respect to executive functioning and vigilant attention throughout sleep deprivation in Val/Val genotype subjects but was hardly effective in subjects with the Met/Met genotype. Neither modafinil nor the Val158Met polymorphism affected distinct markers of sleep homeostasis in recovery sleep. In conclusion, dopaminergic mechanisms contribute to impaired waking functions after sleep loss. |
| Databáze: | OpenAIRE |
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