Chappell P B, Leckman J F, Scahill L D, Hardin M T, Anderson G, Cohen D J
Yale Child Study Center, New Haven, CT 06510-8009.
Psychiatry Res. 1993 Jun;47(3):267-80. doi: 10.1016/0165-1781(93)90084-t.
To evaluate the role of opioids in Tourette's syndrome (TS), we performed a dose-response study of the behavioral and neuroendocrine effects of the selective kappa agonist spiradoline mesylate (U-62066E) in five TS patients and five normal control subjects, aged 20 to 47. The intramuscularly administered doses of spiradoline were 0.0, 0.8, 1.6, and 3.2 micrograms/kg. Baseline and postdrug tic frequencies were determined from "blind" videotape tic counts and bedside clinician ratings. In comparison with placebo, the lowest dose of spiradoline was associated with significant decreases in cumulative postdrug counts of total tics and phonic tics, as well as in clinician ratings of postdrug motor tic frequencies. By contrast, there was a trend for tic frequencies to increase following the intermediate dose (1.6 micrograms/kg) of spiradoline. As a group, the TS subjects also secreted significantly more growth hormone following the 1.6 micrograms/kg dose of spiradoline than did the normal control subjects. These preliminary findings provide additional evidence for the involvement of opioids in TS and suggest (1) that opioids may exert dual modulatory effects on the expression of tic symptoms and (2) that some TS patients may be characterized by increased sensitivity of kappa receptors regulating growth hormone secretion.
为评估阿片类药物在抽动秽语综合征（TS）中的作用，我们对5例年龄在20至47岁的TS患者和5例正常对照者进行了一项关于选择性κ激动剂甲磺酸spiradoline（U - 62066E）行为和神经内分泌效应的剂量反应研究。spiradoline的肌肉注射剂量为0.0、0.8、1.6和3.2微克/千克。通过“盲法”录像抽动计数和床边临床医生评分来确定基线和用药后的抽动频率。与安慰剂相比，最低剂量的spiradoline与用药后总抽动和发声抽动的累积计数显著减少以及临床医生对用药后运动抽动频率的评分降低有关。相比之下，spiradoline中间剂量（1.6微克/千克）后抽动频率有增加的趋势。作为一个群体，TS受试者在接受1.6微克/千克剂量的spiradoline后分泌的生长激素也明显多于正常对照者。这些初步发现为阿片类药物参与TS提供了更多证据，并表明（1）阿片类药物可能对抽动症状的表达产生双重调节作用，以及（2）一些TS患者可能具有调节生长激素分泌的κ受体敏感性增加的特征。
