Phillips M A, Szabadi E, Bradshaw C M
Division of Psychiatry, University of Nottingham, UK.
J Psychopharmacol. 1999 Dec;13(4):391-7. doi: 10.1177/026988119901300410.
We investigated the effects of two 5-HT1A receptor agonists, buspirone and lesopitron, upon pupil size in human volunteers at an ambient luminance level of 32 Cd m(-2) and in darkness. Pupil diameter was monitored with a binocular infrared television pupillometer, before and after the administration of treatments for 4 h at 20-min intervals. Two experiments were conducted. In Experiment 1, 14 healthy male volunteers participated in seven weekly sessions, each associated with the ingestion of one capsule (buspirone 5, 10 and 20 mg, lesopitron 10, 20 and 40 mg and placebo), according to a double-blind balanced, cross-over design. Both buspirone and lesopitron tended to decrease pupil diameter. In darkness, only the highest dose of buspirone (20 mg) caused a miosis that was statistically significant. However, at the luminance level of 32 Cd m(-2) buspirone 10 and 20 mg evoked statistically significant miotic effects, as did the highest dose of lesopitron (40 mg). The miotic effect was significantly greater at 32 Cd m(-2) than in darkness after each dose of buspirone and the highest dose (40 mg) of lesopitron. In Experiment 2, pupil diameter and oral temperature were monitored with an electronic thermometer at 40-min intervals. Twenty healthy male volunteers participated in two weekly sessions, each associated with the sublingual application of 100 microl hydroalcoholic solution (lesopitron 20 mg, placebo), according to a double-blind balanced cross-over design. Lesopitron caused a significant miosis both in darkness and at the luminance level of 32 Cd m(-2); the miosis was greater at 32 Cd m(-2) than in darkness. Lesopitron tended to decrease oral temperature; this effect however, was not statistically significant. The greater effectiveness on the pupil of lesopitron administered sublingually in a solution indicates the importance of first-pass metabolism in reducing the effectiveness of the drug when administered by the mouth. The miosis observed in both experiments may be due to either a sympatholytic or a parasympathomimetic effect of the drugs, or both. The light-dependence of the miosis indicates that the 5-HT1A receptor agonists can modulate the light reflex, possibly via the noradrenergic control of central cholinergic neurones in the Edinger-Westphal nucleus.
我们研究了两种5-羟色胺1A（5-HT1A）受体激动剂丁螺环酮和来索匹隆，在环境亮度为32坎德拉每平方米（Cd m(-2)）以及黑暗条件下，对人类志愿者瞳孔大小的影响。在给药前后，使用双目红外电视瞳孔计，每隔20分钟监测一次瞳孔直径，持续4小时。进行了两项实验。在实验1中，14名健康男性志愿者按照双盲平衡交叉设计，每周参加7次实验，每次服用一粒胶囊（丁螺环酮5毫克、10毫克和20毫克，来索匹隆10毫克、20毫克和40毫克以及安慰剂）。丁螺环酮和来索匹隆都倾向于减小瞳孔直径。在黑暗中，只有最高剂量的丁螺环酮（20毫克）引起的瞳孔缩小具有统计学意义。然而，在亮度为32 Cd m(-2)时，10毫克和20毫克的丁螺环酮以及最高剂量的来索匹隆（40毫克）都引起了具有统计学意义的缩瞳效应。每次服用丁螺环酮以及来索匹隆最高剂量（40毫克）后，在32 Cd m(-2)时的缩瞳效应明显大于黑暗中的效应。在实验2中，每隔40分钟用电子温度计监测瞳孔直径和口腔温度。20名健康男性志愿者按照双盲平衡交叉设计，每周参加2次实验，每次舌下含服100微升水醇溶液（来索匹隆20毫克、安慰剂）。来索匹隆在黑暗中和亮度为32 Cd m(-2)时都引起了显著的瞳孔缩小；在32 Cd m(-2)时的缩瞳效应大于黑暗中的效应。来索匹隆倾向于降低口腔温度；然而，这种效应没有统计学意义。来索匹隆以溶液形式舌下给药时对瞳孔的更大效果表明，首过代谢在口服给药时降低药物效果方面具有重要作用。在两项实验中观察到的瞳孔缩小可能是由于药物的抗交感神经作用或拟副交感神经作用，或者两者兼有。瞳孔缩小对光的依赖性表明，5-HT1A受体激动剂可能通过对动眼神经核中去甲肾上腺素能控制的中枢胆碱能神经元的调节，来调节光反射。
