Raparti Girish, Jain Suyog, Ramteke Karuna, Murthy Mangala, Ghanghas Ravi, Ramanand Sunita, Ramanand Jaiprakash
Department of Pharmacology, Government Medical College, Miraj, Maharashtra, India.
Indian J Endocrinol Metab. 2013 Mar;17(2):211-8. doi: 10.4103/2230-8210.109663.
Thyroid hormone (TH) is known to have many beneficial effects on vital organs, but its extrapolation to be used therapeutically has been restricted by the fact that it does have concurrent adverse effects. Recent finding of various thyroid hormone receptors (TR) isoforms and their differential pattern of tissue distribution has regained interest in possible use of TH analogues in therapeutics. These findings were followed by search of compounds with isoform-specific or tissue-specific action on TR. Studying the structure-activity relationship of TR led to the development of compounds like GC1 and KB141, which preferentially act on the β1 isoform of TR. More recently, eprotirome was developed and has been studied in humans. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity. Another compound, 3,5-diiodothyropropionic acid (DITPA), binds to both α- and β-type TRs with relatively low affinity and has been shown to be effective in heart failure (HF). In postinfarction models of HF and in a pilot clinical study, DITPA increased cardiac performance without affecting the heart rate. TR antagonists like NH3 can be used in thyrotoxicosis and cardiac arrhythmias. However, further larger clinical trials on some of these promising compounds and development of newer compounds with increased selectivity is required to achieve higher precision of action and avoid adverse effects seen with TH.
甲状腺激素（TH）对重要器官具有多种有益作用，但其在治疗上的应用受到其存在不良反应这一事实的限制。最近发现了各种甲状腺激素受体（TR）亚型及其不同的组织分布模式，这重新引发了人们对TH类似物在治疗中可能应用的兴趣。这些发现之后，人们开始寻找对TR具有亚型特异性或组织特异性作用的化合物。对TR结构-活性关系的研究导致了GC1和KB141等化合物的开发，这些化合物优先作用于TR的β1亚型。最近，依普罗胺已被开发并在人体中进行了研究。它已被证明通过TH在肝脏中的降脂作用对血脂异常有效，对肥胖症也有效。另一种化合物3,5-二碘甲状腺丙酸（DITPA）以相对较低的亲和力与α型和β型TR结合，并已被证明对心力衰竭（HF）有效。在心肌梗死后HF模型和一项初步临床研究中，DITPA提高了心脏功能而不影响心率。像NH3这样的TR拮抗剂可用于甲状腺毒症和心律失常。然而，需要对一些这些有前景的化合物进行进一步的大规模临床试验，并开发出选择性更高的新化合物，以实现更高的作用精度并避免TH所见的不良反应。
