| Does modafinil activate the locus coeruleus in man? Comparison of modafinil and clonidine on arousal and autonomic functions in human volunteers. | |
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MedLine Citation:
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PMID: 15983798 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Modafinil 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. OBJECTIVE: The aim of the study is to compare the effects of single doses of modafinil and clonidine on arousal and autonomic functions in human volunteers. METHODS: Sixteen 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. RESULTS: Clonidine 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. CONCLUSIONS: Clonidine 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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Authors:
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R H Hou; C Freeman; R W Langley; E Szabadi; C M Bradshaw |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial Date: 2005-10-12 |
Journal Detail:
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Title: Psychopharmacology Volume: 181 ISSN: 0033-3158 ISO Abbreviation: Psychopharmacology (Berl.) Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-10-21 Completed Date: 2006-02-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7608025 Medline TA: Psychopharmacology (Berl) Country: Germany |
Other Details:
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Languages: eng Pagination: 537-49 Citation Subset: IM |
Affiliation:
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Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic alpha-Agonists
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pharmacology* Adult Arousal / drug effects* Autonomic Nervous System / drug effects* Benzhydryl Compounds / pharmacology* Blood Pressure / drug effects Central Nervous System Stimulants / pharmacology* Clonidine / pharmacology* Cross-Over Studies Double-Blind Method Flicker Fusion Heart Rate / drug effects Humans Locus Coeruleus / drug effects* Male Norepinephrine / metabolism Reflex, Pupillary / drug effects Salivation / drug effects Sympatholytics / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-Agonists; 0/Benzhydryl Compounds; 0/Central Nervous System Stimulants; 0/Sympatholytics; 4205-90-7/Clonidine; 51-41-2/Norepinephrine; 68693-11-8/modafinil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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