Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine.
OBJECTIVE
To examine the relationship between sedation and pupillary function by comparing the effects of diazepam and diphenhydramine on arousal and pupillary activity.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Hou
Ruihua H
RH
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, UK.
Scaife
Jessica
J
Freeman
Clare
C
Langley
Rob W
RW
Szabadi
Elemer
E
Bradshaw
Chris M
CM
D000293:Adolescent; D000328:Adult; D001143:Arousal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005425:Flicker Fusion; D005712:Galvanic Skin Response / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D009184:Mydriatics / Q000494:pharmacology*; D010775:Photic Stimulation; D011680:Pupil / Q000187:drug effects*; D012025:Reflex, Pupillary / Q000187:drug effects
D006993:Hypnotics and Sedatives; D009184:Mydriatics; D004155:Diphenhydramine; D003975:Diazepam