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酮色林、丁螺环酮和普萘洛尔对健康志愿者觉醒、瞳孔大小及自主神经功能的比较。

Comparison of ketanserin, buspirone and propranolol on arousal, pupil size and autonomic function in healthy volunteers.

作者信息

Koudas Vassilis, Nikolaou Alexandra, Hourdaki Eugenia, Giakoumaki Stella G, Roussos Panos, Bitsios Panos

机构信息

Department of Psychiatry & Behavioral Sciences, Medical School, University of Crete, P.O. Box 2208, Heraklion, 71003, Crete, Greece.

出版信息

Psychopharmacology (Berl). 2009 Jul;205(1):1-9. doi: 10.1007/s00213-009-1508-5. Epub 2009 Mar 14.

DOI:10.1007/s00213-009-1508-5
PMID:19288084
Abstract

RATIONALE

The human pupil may be a suitable physiological test system for the assessment of excessive daytime sleepiness (EDS), but pupillometric assessment could be confounded by medication for comorbid hypertension and mood disorders.

OBJECTIVES

We examined the profile of the 5HT-2/alpha1/H1 antagonist ketanserin, the 5HT1a agonist buspirone and the beta adrenoceptor antagonist propranolol on pupillary and other measures of arousal.

MATERIALS AND METHODS

Ketanserin (20 mg), buspirone (10 mg) and propranolol (40 mg) were administered in three independent experiments according to a crossover, placebo-controlled, double-blind design. Resting pupil diameter (RPD) was sampled over 5-min in darkness with infrared pupillometry. Tests also included critical flicker fusion frequency (CFFF), visual analogue scales (VAS), the pupillary light reflex and heart rate/blood pressure.

RESULTS

Ketanserin reduced RPD, CFFF, VAS-rated arousal and blood pressure and increased the light reflex amplitude. Buspirone reduced RPD and blood pressure. Propranolol reduced heart rate but had no effects on pupillary functions or any arousal measure.

CONCLUSIONS

Ketanserin but not propranolol had a fully sedative profile and may confound pupillometric assessment of EDS. Beta adrenergic receptors do not appear to participate in arousal and pupillary functions, while 5HT1a receptors reduce pupil size without affecting arousal. Pupil size may not be used unequivocally as an index of the level of alertness in the case of drug-induced changes, when drugs interfere with the central pupil control mechanism in ways that are unrelated to their effects on arousal.

摘要

理论依据

人眼瞳孔可能是评估日间过度嗜睡(EDS)的合适生理测试系统,但瞳孔测量评估可能会因用于治疗合并存在的高血压和情绪障碍的药物而受到干扰。

目的

我们研究了5-羟色胺-2/α1/H1拮抗剂酮色林、5-羟色胺1a激动剂丁螺环酮和β肾上腺素能受体拮抗剂普萘洛尔对瞳孔及其他觉醒指标的影响。

材料与方法

根据交叉、安慰剂对照、双盲设计,在三个独立实验中分别给予酮色林(20毫克)、丁螺环酮(10毫克)和普萘洛尔(40毫克)。在黑暗环境中使用红外瞳孔测量法,在5分钟内采集静息瞳孔直径(RPD)。测试还包括临界闪烁融合频率(CFFF)、视觉模拟量表(VAS)、瞳孔对光反射以及心率/血压。

结果

酮色林降低了RPD、CFFF、VAS评定的觉醒程度和血压,并增加了光反射幅度。丁螺环酮降低了RPD和血压。普萘洛尔降低了心率,但对瞳孔功能或任何觉醒指标均无影响。

结论

酮色林具有完全的镇静作用,而普萘洛尔则没有,酮色林可能会干扰对EDS的瞳孔测量评估。β肾上腺素能受体似乎不参与觉醒和瞳孔功能,而5-羟色胺1a受体可减小瞳孔大小而不影响觉醒。在药物引起变化的情况下,当药物以与其对觉醒的影响无关的方式干扰中枢瞳孔控制机制时,瞳孔大小可能不能明确用作警觉水平的指标。

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