Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers

• Published in: Journal of psychopharmacology (Oxford) 2006-11, Vol.20 (6), p.756-770
• Main Authors: Samuels, E. R., Hou, R. H., Langley, R. W., Szabadi, E., Bradshaw, C. M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Arousal - drug effects; Autonomic Nervous System - drug effects; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - pharmacology; Benzothiazoles - adverse effects; Benzothiazoles - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Body Temperature - drug effects; Brain; Central Nervous System Stimulants - adverse effects; Central Nervous System Stimulants - pharmacology; Comparative analysis; Comparative studies; Complications and side effects; Dopamine Agonists - adverse effects; Dopamine Agonists - pharmacology; Dosage and administration; Double-Blind Method; Drug Interactions; Drug therapy; Endocrine System - drug effects; Flicker Fusion - drug effects; Heart Rate - drug effects; Human Growth Hormone - blood; Humans; Male; Medical sciences; Modafinil; Narcolepsy; Neuropharmacology; Patient outcomes; Pharmacology. Drug treatments; Pramipexole; Prolactin - blood; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Psychotropic drugs; Pupil - drug effects; Salivation - drug effects; Side effects; Sleep; Thyrotropin - blood
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881106060770

The noradrenergic locus coeruleus is a major wakefulness-promoting nucleus of the brain, which is also involved in the regulation of autonomic and endocrine functions. The activity of the locus coeruleus is believed to be tonically enhanced by a mesocoerulear dopaminergic pathway arising from the ventral tegmental area of the midbrain. Both modafinil, a wakefulness-promoting drug, and pramipexole, a D2/D3receptor agonist with sedative properties, may act on this pathway, with modafinil increasing and pramipexole decreasing locus coeruleus activity. The aim of this study was to compare the two drugs on alertness, autonomic and endocrine functions in healthy volunteers. Pramipexole (0.5mg), modafinil (200mg), and their combination were administered to 16 healthy males in a double-blind, placebo-controlled design. Methods included tests of alertness (pupillographic sleepiness test, critical flicker fusion frequency, visual analogue scales), autonomic functions (resting pupil diameter, light and darkness reflex responses, heart rate, blood pressure, salivation, core temperature), and endocrine functions (blood concentrations of prolactin, growth hormone, and thyroid stimulating hormone). Data were analysed by ANOVA. Pramipexole reduced alertness, caused pupil dilatation, increased heart rate, reduced prolactin and thyroid stimulating hormone, and increased growth hormone level. Modafinil caused small increases in blood pressure and core temperature, and reduced prolactin levels. The sedative effect of pramipexole and the autonomic effects of modafinil are consistent with altered activity in the mesocoerulear pathway; the pupil dilatation following pramipexole suggests reduced dopaminergic excitation of the Edinger-Westphal nucleus.