Peuckmann V, Fisch M, Bruera E
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Drugs. 2000 Aug;60(2):273-92. doi: 10.2165/00003495-200060020-00003.
Thalidomide, after being banned from the market in the early 1960s because of the worldwide teratogenesis disaster, is currently being rediscovered because of its multiple therapeutic effects in various serious diseases and symptoms. Original studies examined the anxiolytic, mild hypnotic, anti-emetic and adjuvant analgesic properties of this drug. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy (erythema nodosum leprosum) and even to be superior to aspirin (acetylsalicylic acid) in controlling leprosy-associated fever. Recent research shows promising results with thalidomide in patients with progressive bodyweight loss related to advanced cancer and HIV infection. Thalidomide therapy of diseases such as tuberculosis, sarcoidosis, aphthous ulcers in HIV syndrome and Behcet's disease, rheumatoid arthritis, multiple myeloma, graft-versus-host disease, pyoderma gangrenosum, inflammatory bowel disease, Sjögren's syndrome, lupus erythematosus and a variety of solid tumours is currently being explored. Furthermore, in preliminary studies, thalidomide has been found to be effective in several syndromes related to advanced cancer, such as the cancer cachexia syndrome, chronic nausea, insomnia, profuse sweating and pain. Whether thalidomide has a therapeutic effect on neoplastic fever has yet to be elucidated. These intriguing features make the use of the drug potentially attractive for palliative care. In addition, by a distinct mechanism of action compared with most other drugs, thalidomide offers the possibility of combined treatment with other agents with non-overlapping toxicities. The mechanism of action of thalidomide is probably based on the suppression of tumour necrosis factor-alpha and the modulation of interleukins. However, it is not possible to identify a single dominant mechanism, since the action of cytokines and the effect of thalidomide appear to be complex. This review article discusses the original uses and teratogenic effects of thalidomide within its historical context and, linking recent research at the molecular level with clinical findings, aims to provide the reader with insight into the current understanding of its biological actions, toxicities and potential benefits.
沙利度胺在20世纪60年代初因全球致畸灾难而被禁市，目前因其在各种严重疾病和症状中的多种治疗作用而被重新发现。最初的研究考察了该药物的抗焦虑、轻度催眠、止吐和辅助镇痛特性。随后，发现沙利度胺在治疗麻风病的皮肤表现（麻风结节性红斑）方面非常有效，甚至在控制麻风相关发热方面优于阿司匹林（乙酰水杨酸）。最近的研究表明，沙利度胺对与晚期癌症和HIV感染相关的进行性体重减轻患者有令人鼓舞的效果。目前正在探索沙利度胺对诸如结核病、结节病、HIV综合征中的阿弗他溃疡和白塞病、类风湿关节炎、多发性骨髓瘤、移植物抗宿主病、坏疽性脓皮病、炎症性肠病、干燥综合征、红斑狼疮以及各种实体瘤等疾病的治疗作用。此外，在初步研究中，已发现沙利度胺对与晚期癌症相关的几种综合征有效，如癌症恶病质综合征、慢性恶心、失眠、多汗和疼痛。沙利度胺对肿瘤热是否有治疗作用尚未阐明。这些引人关注的特性使得该药物在姑息治疗中具有潜在吸引力。此外，与大多数其他药物相比，沙利度胺具有独特的作用机制，提供了与其他毒性不重叠的药物联合治疗的可能性。沙利度胺的作用机制可能基于对肿瘤坏死因子-α的抑制和白细胞介素的调节。然而，由于细胞因子的作用和沙利度胺的效应似乎很复杂，无法确定单一的主导机制。这篇综述文章在其历史背景下讨论了沙利度胺的最初用途和致畸作用，并将分子水平的最新研究与临床发现联系起来，旨在让读者深入了解目前对其生物学作用、毒性和潜在益处的认识。
