Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo, 669, Vila Clementino, São Paulo, SP, 04039-032, Brazil.
Pharmacol Res. 2019 Mar;141:298-302. doi: 10.1016/j.phrs.2019.01.008. Epub 2019 Jan 9.
Many reports have been demonstrating off-label effects for calcium (Ca) channel blockers (CCBs), for example: patients medicated with CCBs have had an improvement of their diabetes status (control of glycemia), along with an improvement of both depression symptoms and cognitive function. Indeed, diabetes and depression are medical problems both with clearly restricted pharmacotherapies, along with a high prevalence around the world, then costing millions and millions for the medical health systems. Furthermore, the incidence of depression is till three times higher in patients with diabetes. In addition, depression may augment the risk of developing type 2 diabetes till 60%. Then, there is a clear "bidirectional link" between depression and diabetes, reflecting substantial interactions in their etiology. But which are the possible cellular mechanisms for this "bidirectional link" between depression and diabetes, and for the off-label effects of CCBs? Considering our previously cited international articles, which demonstrated the role of the Ca/cAMP signalling in regulating both the neurotransmitter release and the neuronal death, in this review I have debated the possible involvement of the Ca/cAMP signalling in the off-label effects of CCBs, including the role of the Ca/cAMP signalling in the "bidirectional link" between diabetes and depression.
许多报告已经证明了钙通道阻滞剂（CCBs）的标签外效应，例如：接受 CCB 治疗的患者的糖尿病状况（血糖控制）得到了改善，同时抑郁症状和认知功能也得到了改善。事实上，糖尿病和抑郁症都是医学问题，其药物治疗受到明显限制，而且在全球范围内患病率很高，这给医疗保健系统带来了数百万甚至数千万的费用。此外，糖尿病患者的抑郁发病率高出三倍。此外，抑郁可能会使患 2 型糖尿病的风险增加 60%。因此，抑郁和糖尿病之间存在明显的“双向联系”，反映了它们在病因学上的实质性相互作用。但是，这种抑郁和糖尿病之间的“双向联系”以及 CCB 的标签外效应的可能细胞机制是什么？考虑到我们之前引用的国际文章，这些文章证明了 Ca/cAMP 信号在调节神经递质释放和神经元死亡中的作用，在这篇综述中，我讨论了 Ca/cAMP 信号在 CCB 的标签外效应中的可能参与，包括 Ca/cAMP 信号在糖尿病和抑郁症之间的“双向联系”中的作用。
