Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers
Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers
Arousal is regulated by the interplay between wakefulness- and sleep-promoting nuclei. Major wakefulness-promoting nuclei are the histaminergic tuberomamillary nucleus (TMN) of the hypothalamus and the noradrenergic locus coeruleus (LC) of the pons, which also play a role in autonomic regulation. First generation antihistamines, such as diphenhydramine, are likely to cause sedation by blocking excitatory H1 histamine receptors in the cerebral cortex, and the anti-narcolepsy drug modafinil may promote wakefulness by activating the locus coeruleus. We compared the effects of single doses of diphenhydramine (75 mg) and modafinil (200 mg) on arousal and autonomic functions in 16 healthy male volunteers, using a placebo-controlled, balanced, double-blind design. Arousal was assessed by critical flicker fusion frequency (CFFF), visual analogue scales (VAS) and pupillary fatigue waves (Pupillographic Sleepiness Test (PST)). Autonomic functions measured included resting pupil diameter, light and darkness reflex responses, blood pressure, heart rate and salivation. Data were analysed with ANOVA, with multiple comparisons. Diphenhydramine had sedative effects as shown by reductions in CFFF, VAS alertness ratings and increases of the indices of pupillary fatigue. Modafinil had alerting effects as indicated by reductions in the measures of pupillary fatigue. Comparison of pre-post medication changes in pupil diameter showed a decrease after diphenhydramine and an increase after modafinil. Diphenhydramine reduced salivation, and modafinil increased systolic blood pressure. In conclusion, diphenhydramine and modafinil evoked opposite effects on arousal and sympathetic functions, which are likely to reflect their interaction with the central histaminergic and noradrenergic systems. Hyposalivation by diphenhydramine is likely to be due to its additional anticholinergic property.
male, pupillary, cross-over studies, salivation, affect, autonomic nervous system, blood, flicker fusion, drug effects, attention, pupil, administration, reflex, fatigue, pharmacology, locus coeruleus
567-578
Hou, R.H.
470bdcbc-93a9-4dad-aac5-26d455c34376
Langley, R.W.
579cc42e-972f-4422-952f-1c76ecc4b4e3
Szabadi, E.
cff688f8-264f-4ca3-a2c4-cb10930f1956
Bradshaw, C.M.
0baafd10-0e91-4113-b90b-27132bd77305
1 August 2007
Hou, R.H.
470bdcbc-93a9-4dad-aac5-26d455c34376
Langley, R.W.
579cc42e-972f-4422-952f-1c76ecc4b4e3
Szabadi, E.
cff688f8-264f-4ca3-a2c4-cb10930f1956
Bradshaw, C.M.
0baafd10-0e91-4113-b90b-27132bd77305
Hou, R.H., Langley, R.W., Szabadi, E. and Bradshaw, C.M.
(2007)
Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers.
Journal of Psychopharmacology, 21 (6), .
(doi:10.1177/0269881106071022).
Abstract
Arousal is regulated by the interplay between wakefulness- and sleep-promoting nuclei. Major wakefulness-promoting nuclei are the histaminergic tuberomamillary nucleus (TMN) of the hypothalamus and the noradrenergic locus coeruleus (LC) of the pons, which also play a role in autonomic regulation. First generation antihistamines, such as diphenhydramine, are likely to cause sedation by blocking excitatory H1 histamine receptors in the cerebral cortex, and the anti-narcolepsy drug modafinil may promote wakefulness by activating the locus coeruleus. We compared the effects of single doses of diphenhydramine (75 mg) and modafinil (200 mg) on arousal and autonomic functions in 16 healthy male volunteers, using a placebo-controlled, balanced, double-blind design. Arousal was assessed by critical flicker fusion frequency (CFFF), visual analogue scales (VAS) and pupillary fatigue waves (Pupillographic Sleepiness Test (PST)). Autonomic functions measured included resting pupil diameter, light and darkness reflex responses, blood pressure, heart rate and salivation. Data were analysed with ANOVA, with multiple comparisons. Diphenhydramine had sedative effects as shown by reductions in CFFF, VAS alertness ratings and increases of the indices of pupillary fatigue. Modafinil had alerting effects as indicated by reductions in the measures of pupillary fatigue. Comparison of pre-post medication changes in pupil diameter showed a decrease after diphenhydramine and an increase after modafinil. Diphenhydramine reduced salivation, and modafinil increased systolic blood pressure. In conclusion, diphenhydramine and modafinil evoked opposite effects on arousal and sympathetic functions, which are likely to reflect their interaction with the central histaminergic and noradrenergic systems. Hyposalivation by diphenhydramine is likely to be due to its additional anticholinergic property.
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Published date: 1 August 2007
Keywords:
male, pupillary, cross-over studies, salivation, affect, autonomic nervous system, blood, flicker fusion, drug effects, attention, pupil, administration, reflex, fatigue, pharmacology, locus coeruleus
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Local EPrints ID: 62421
URI: http://eprints.soton.ac.uk/id/eprint/62421
ISSN: 0269-8811
PURE UUID: 9592efcc-ae63-4839-a2be-5003a0d9ced6
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Date deposited: 12 Sep 2008
Last modified: 16 Mar 2024 03:55
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Author:
R.W. Langley
Author:
E. Szabadi
Author:
C.M. Bradshaw
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