Guiloff R J
Department of Neurology, Westminster Hospital, Charing Cross and Westminster Medical School, London, United Kingdom.
Ann N Y Acad Sci. 1989;553:399-421. doi: 10.1111/j.1749-6632.1989.tb46662.x.
TRH analogues have a longer half-life than does TRH and enhanced neuropharmacological actions. In motorneurone disease (MND), no benefit was reported with MK771 and DN1417. Focal, transient, and slight improvements in weakness and spasticity were described with CG3509. A controlled trial with a single intravenous dose of RX 77368 showed improvements in dysarthria, tongue movements, respiration, swallowing, and spasticity lasting up to 72 hours. Changes in muscle force were of no functional significance. There was an acute 25-30% increase in mean corrected fiber density and in mean macro-EMG parameters in biceps, but no change in amplitude or area of single macro-EMG motor units followed during the 2-hour infusions. An acute, direct or indirect, central effect of RX77368 on recruitment order or on activation threshold of pathological motor units is suggested. In a subacute open trial with repeated intravenous infusions of RX77368 (median 2 weeks), improvement in bulbar function in 8 of 12 responders, cramps (5 of 9), and spasticity (5 of 8) were maintained for medians of 18, 14, and 7 days, respectively. Side effects were prominent with doses above 0.2 mg/kg. Disease progression has not been halted with any analogue, but whether it may be usefully slowed down with RX77368 is worth investigating.
促甲状腺激素释放激素（TRH）类似物的半衰期比TRH长，且具有增强的神经药理学作用。在运动神经元病（MND）中，MK771和DN1417未显示出益处。CG3509可使无力和痉挛有局部、短暂及轻微改善。一项单次静脉注射RX 77368的对照试验显示，构音障碍、舌运动、呼吸、吞咽及痉挛均有改善，持续长达72小时。肌肉力量的变化无功能意义。二头肌的平均校正纤维密度和平均巨肌电图参数急性增加25% - 30%，但在2小时输注期间，单个巨肌电图运动单位的幅度或面积无变化。提示RX77368对募集顺序或病理性运动单位的激活阈值有急性、直接或间接的中枢作用。在一项对RX77368进行重复静脉输注的亚急性开放试验（中位数为2周）中，12名有反应者中的8名球部功能改善、9名中的5名痉挛及8名中的5名抽筋分别维持了中位数18天、14天和7天。剂量高于0.2mg/kg时副作用明显。尚无任何类似物能阻止疾病进展，但RX77368是否能有效减缓疾病进展值得研究。
