van Ruitenbeek P, Vermeeren A, Smulders F T Y, Sambeth A, Riedel W J
Experimental Psychopharmacology Unit, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Br J Pharmacol. 2009 May;157(1):76-85. doi: 10.1111/j.1476-5381.2008.00103.x. Epub 2009 Feb 13.
Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia.
Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three-way, double-blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event-related potentials.
Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event-related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times.
The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target.
中枢活性抗组胺药会损害认知表现，尤其是感觉运动表现。本研究的目的是进一步阐明在感觉运动表现中较少被研究的子过程，这些子过程可能会受到H1受体阻断的影响。更好地了解与组胺功能障碍相关的认知缺陷有助于更好地治疗组胺功能减退可能是一个促成因素的临床疾病，如精神分裂症。
研究了右氯苯那敏在选择反应时任务中与特定任务操作的相互作用。通过降低刺激质量在感觉子过程层面增加任务需求，通过增加反应复杂性在运动子过程层面增加任务需求。共有18名年龄在18至45岁之间的健康志愿者（9名女性）参与了一项三因素、双盲、交叉设计。治疗方法为单次口服4毫克右氯苯那敏、1毫克劳拉西泮和安慰剂。通过测量反应时间评估行为效应，通过事件相关电位评估对脑活动的影响。
右氯苯那敏显著延长了反应时间，但与任务操作没有显著的相互作用。然而，通过事件相关电位测量，它与刺激质量有显著的相互作用。劳拉西泮延长了反应时间，并与知觉操作有相互作用，这从对反应时间的影响中可以看出。
结果证实组胺系统参与感觉信息处理，并表明H1受体阻断不影响运动信息处理。临床疾病中的组胺功能减退可能导致感觉处理受损，这可能是一个药物靶点。
