Related Experiment Video
Updated: Jun 27, 2026

Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Pharmacogenetics of modafinil after sleep loss: catechol-O-methyltransferase genotype modulates waking functions but
S Bodenmann1, S Xu, U F O Luhmann
1Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
Abstract:
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.
Related Concept Videos
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Substance Use Disorders Affecting Sleep
Understanding the concepts of physical dependence,...
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

