Müller Thomas
St. Joseph Hospital Berlin-Weißensee, Department of Neurology , Gartenstr. 1, 13088 Berlin , Germany +49 30 92790223 ; +49 30 92790703 ;
Expert Opin Investig Drugs. 2015 Jun;24(6):737-42. doi: 10.1517/13543784.2015.1029573. Epub 2015 Mar 25.
The chronic use and high dosing of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics predispose patients to the onset of tardive syndromes. One particular subtype, tardive dyskinesia, is characterized by rapid, repetitive, stereotypic, involuntary movements of the face, limbs or trunk. The inhibition of the vesicular monoamine transporter system, using tetrabenazine therapy, improves the severity of tardive dyskinesia. But there are also drawbacks to tetrabenazine treatment, such as a fluctuating response and the need for frequent intake due to its rapid metabolism. Clinical research on the potentially more efficacious and easier to use tetrabenazine analogs is already under way. One of them is valbenazine, the purified parent drug of the (+)-α-isomer of tetrabenazine. The FDA lowered approval hurdles for valbenazine due to a successful Phase II trial, which showed a distinctive improvement in tardive dyskinesia symptoms during valbenazine administration. This resurgence in the clinical research of tardive syndrome therapy is most welcome. This author notes that the putative long-term side effects of valbenazine should carefully be investigated in the future via naturalistic observational trials. Furthermore, valbenazine may also support the onset of symptoms, such as Parkinsonism and depression, with chronic administration, as it, to a certain extent, shares the mode of action of tetrabenazine.
长期使用高剂量的典型抗精神病药物或中枢作用的多巴胺受体阻断性止吐药会使患者易患迟发性综合征。其中一种特殊亚型，迟发性运动障碍，其特征是面部、四肢或躯干出现快速、重复、刻板、不自主的运动。使用丁苯那嗪治疗抑制囊泡单胺转运体系统可改善迟发性运动障碍的严重程度。但丁苯那嗪治疗也存在缺点，如反应波动以及由于其快速代谢需要频繁服药。关于可能更有效且更易于使用的丁苯那嗪类似物的临床研究已经在进行中。其中之一是缬苯那嗪，它是丁苯那嗪（+）-α-异构体的纯化母体药物。由于一项成功的II期试验，美国食品药品监督管理局降低了缬苯那嗪的审批门槛，该试验表明在服用缬苯那嗪期间迟发性运动障碍症状有明显改善。迟发性综合征治疗临床研究的这种复兴是非常受欢迎的。本文作者指出，缬苯那嗪假定的长期副作用未来应通过自然观察性试验仔细研究。此外，缬苯那嗪长期给药可能也会引发帕金森症和抑郁症等症状，因为它在一定程度上与丁苯那嗪的作用方式相同。
