Trial reportPsychopharmacology2005
Does modafinil activate the locus coeruleus in man? Comparison of modafinil and clonidine on arousal and autonomic functions in human volunteers.
Trial report in Psychopharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 124 citations in OpenAlex.
- Stimulating meditation: a pre-registered randomised controlled experiment combining a single dose of the cognitive enhancer, modafinil, with brief mindfulness training.Journal of psychopharmacology (Oxford, England) · 2021Trial
- The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial.Neuro-oncology · 2013Trial
- Effects of acute modafinil on cognition in trichotillomania.Psychopharmacology · 2010Trial
- Lack of sedative effects after vespertine intake of oxazepam as hypnotic in healthy volunteers.Psychopharmacology · 2009Trial
- Comparison of ketanserin, buspirone and propranolol on arousal, pupil size and autonomic function in healthy volunteers.Psychopharmacology · 2009Trial
- Arousal and the pupil: why diazepam-induced sedation is not accompanied by miosis.Psychopharmacology · 2007Trial
- Comparison of pramipexole and amisulpride on alertness, autonomic and endocrine functions in healthy volunteers.Psychopharmacology · 2006Trial
- The Pupil-Brain System at Rest: Spontaneous Pupil Fluctuations as Markers of Neuromodulatory and Network Dynamics.Psychophysiology · 2026Review
- The Contribution of the Locus Ceruleus-Norepinephrine System to the Coupling between Pupil-Linked Arousal and Cortical State.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The Efficacy of Melatonergic Receptor Agonists Used in Clinical Practice in Insomnia Treatment: Melatonin, Tasimelteon, Ramelteon, Agomelatine, and Selected Herbs.Molecules (Basel, Switzerland) · 2025Review
- Functional neuroanatomy of dopaminergic arousal systems: implications for the wake-promoting effect of psychostimulants, with particular reference to modafinil.Frontiers in neuroanatomy · 2025Review
- Impact of Stimulation Duration in taVNS-Exploring Multiple Physiological and Cognitive Outcomes.Brain sciences · 2024Article
- Impact of acute psychosocial stress on attentional control in humans. A study of evoked potentials and pupillary response.Neurobiology of stress · 2023Article
- Tonic and phasic effects of reward on the pupil: implications for locus coeruleus function.Proceedings. Biological sciences · 2022Article
- Superior frontal regions reflect the dynamics of task engagement and theta band-related control processes in time-on task effects.Scientific reports · 2022Article
- Time-On-Task Effects on Working Memory Gating Processes-A Role of Theta Synchronization and the Norepinephrine System.Cerebral cortex communications · 2022Article
- The peripheral effect of direct current stimulation on brain circuits involving memory.Science advances · 2020Article
- Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection.Neuropharmacology · 2020Article
- Component processes in free-viewing visual search: Insights from fixation-aligned pupillary response averaging.Journal of vision · 2020Article
- How the depth of processing modulates emotional interference - evidence from EEG and pupil diameter data.Cognitive, affective & behavioral neuroscience · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleModafinil is a wakefulness-promoting drug which is likely to activate some wakefulness-promoting and/or inhibit sleep-promoting neurones in the brain. The locus coeruleus (LC) is a wakefulness-promoting noradrenergic nucleus whose activity can be "switched off" by the alpha2-adrenoceptor agonist clonidine, leading to sedative and sympatholytic effects.
objectiveThe aim of the study is to compare the effects of single doses of modafinil and clonidine on arousal and autonomic functions in human volunteers.
methodsSixteen healthy male volunteers participated in four experimental sessions (modafinil 200 mg; clonidine 0.2 mg; modafinil 200 mg + clonidine 0.2 mg; placebo) at weekly intervals, according to a balanced double-blind protocol. Arousal [pupillary "fatigue waves" (PFW), critical flicker fusion frequency, self-ratings of alertness] and autonomic functions (pupil diameter, pupillary light and darkness reflex responses, blood pressure, heart rate, salivation) were recorded. Data were analyzed with ANOVA, with multiple comparisons.
resultsClonidine reduced subjective alertness, pupil diameter, the initial velocity and amplitude of the darkness reflex response, systolic and diastolic blood pressure and salivation, prolonged the recovery time of the light reflex response and increased PFW. Modafinil reduced PFW, increased pupil diameter and the initial velocity of the darkness reflex response and tended to reduce the effect of clonidine on pupil diameter and PFW. Modafinil had no effect on non-pupillary autonomic functions.
conclusionsClonidine exerted sympatholytic and sedative effects, whereas modafinil had sympathomimetic and some alerting effects. Modafinil may activate noradrenergic neurones in the LC involved in arousal and pupillary control, without affecting extracoerulear noradrenergic neurones involved in cardiovascular and salivary regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.