Hou Ruihua H, Scaife Jessica, Freeman Clare, Langley Rob W, Szabadi Elemer, Bradshaw Chris M
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, UK.
Br J Clin Pharmacol. 2006 Jun;61(6):752-60. doi: 10.1111/j.1365-2125.2006.02632.x.
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.
通过比较地西泮和苯海拉明对觉醒和瞳孔活动的影响，探讨镇静与瞳孔功能之间的关系。
15名男性志愿者参加了为期三周的实验，根据平衡双盲方案，他们分别接受（i）10mg地西泮、（ii）75mg苯海拉明和（iii）安慰剂。在四个亮度水平下，用红外瞳孔测量法测量瞳孔直径。通过视觉模拟量表（VAS）和临界闪烁融合频率（CFFF）评估警觉性。用传统方法记录血压、心率和皮肤电导率。数据采用方差分析（anova）和多重比较进行分析。
环境亮度（F3,42 = 305.7，P < 0.001）和治疗条件（F2,28 = 9.0，P < 0.01）对瞳孔直径有显著影响；苯海拉明在所有亮度水平下均引起瞳孔缩小（P < 0.05）。光反射反应未受影响。与安慰剂相比，两种活性药物均降低了治疗前后的变化[与安慰剂的平均差异（95%置信区间）]：在CFFF（Hz）方面，地西泮为-0.73（-1.63，0.17），苯海拉明为-1.46（-2.40，-0.52）；在VAS警觉性（mm）方面，地西泮为-11.49（-19.19，-3.79），苯海拉明为-19.83（-27.46，-12.20）。实验阶段（F2,26 = 145.1，P < 0.001）和治疗（F2,26 = 5.5，P < 0.01）对皮肤电导率均有显著影响；两种药物均降低了皮肤电导率（P < 0.05）。
苯海拉明引起的瞳孔缩小以及两种药物引起的皮肤电导率降低可能表明有中枢抗交感神经作用。地西泮对瞳孔缺乏抗交感神经作用可能是由于抑制虹膜副交感神经输出导致的散瞳掩盖了瞳孔缩小。
