Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine
Article first published online: 27 FEB 2006
British Journal of Clinical Pharmacology
Volume 61, Issue 6, pages 752–760, June 2006
How to Cite
Hou, R. H., Scaife, J., Freeman, C., Langley, R. W., Szabadi, E. and Bradshaw, C. M. (2006), Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine. British Journal of Clinical Pharmacology, 61: 752–760. doi: 10.1111/j.1365-2125.2006.02632.x
- Issue published online: 27 FEB 2006
- Article first published online: 27 FEB 2006
- Received 10 October 2005 Accepted 16 December 2005
- light reflex;
- skin conductance
To examine the relationship between sedation and pupillary function by comparing the effects of diazepam and diphenhydramine on arousal and pupillary activity.
Fifteen male volunteers participated in three weekly sessions in which they received (i) diazepam 10 mg, (ii) diphenhydramine 75 mg and (iii) placebo, according to a balanced, double-blind protocol. Pupil diameter was measured with infrared pupillometry under four luminance levels. Alertness was assessed by visual analogue scales (VAS) and by critical flicker fusion frequency (CFFF). Blood pressure, heart rate and skin conductance were recorded by conventional methods. Data were analysed with analysis of variance (anova) with multiple comparisons.
There were significant effects of ambient luminance (F3,42 = 305.7, P < 0.001) and treatment condition (F2,28 = 9.0, P < 0.01) on pupil diameter; diphenhydramine caused miosis at all luminance levels (P < 0.05). The light reflex response was not affected. Both active drugs reduced the pre-post treatment changes compared with placebo [mean difference from placebo (95% confidence interval)]: in CFFF (Hz), diazepam −0.73 (−1.63, 0.17), diphenhydramine −1.46 (−2.40, −0.52); and VAS alertness (mm), diazepam −11.49 (−19.19, −3.79), diphenhydramine −19.83 (−27.46, −12.20). There were significant effects of both session (F2,26 = 145.1, P < 0.001) and treatment (F2,26 = 5.5, P < 0.01) on skin conductance; skin conductance was reduced by both drugs (P < 0.05).
The miosis by diphenhydramine and the reduction in skin conductance by both drugs may indicate central sympatholytic effects. A lack of a sympatholytic effect of diazepam on the pupil may be due to the masking of the miosis by mydriasis resulting from the inhibition of the parasympathetic output to the iris.