Department of Neurology, Sleep Division, Massachusetts General Hospital, Wang Ambulatory Center 7th Floor, Boston, MA 02114, USA.
Med Hypotheses. 2010 Feb;74(2):297-300. doi: 10.1016/j.mehy.2009.09.003. Epub 2009 Sep 27.
There is growing interest in the concept of network pharmacology, as opposed to specific pharmacological targets, as an important drug discovery paradigm. Also known as the "magic shotgun" paradigm, this strategy involves individual drugs interacting with multiple targets to achieve clinical benefit. Pharmacological promiscuity consistent with this paradigm has been suggested in vitro for antidepressants and anticonvulsants, which interact with many classes of ion channels (among other receptor targets). Although the link between certain "off-target" interactions and drug side effects is well-accepted, the potential linkage between promiscuity and clinical efficacy remains poorly understood. Here we summarize interactions of clinically useful anti-psychotic and anti-dementia medications with a diverse array of ligand- and voltage-gated ion channels. We hypothesize that promiscuous ion channel modulation may contribute to the efficacy of drugs used to treat psychosis and dementia.
人们对网络药理学的概念越来越感兴趣，与特定的药理靶点相比，它是一种重要的药物发现范式。也被称为“神奇猎枪”范式，这种策略涉及到单个药物与多个靶点相互作用，以达到临床获益。体外研究表明，抗抑郁药和抗惊厥药具有这种药理学混杂性，它们与许多类别的离子通道（以及其他受体靶点）相互作用。尽管某些“非靶点”相互作用与药物副作用之间的联系已被广泛接受，但混杂性与临床疗效之间的潜在联系仍知之甚少。在这里，我们总结了临床上有用的抗精神病药和抗痴呆药与各种配体门控和电压门控离子通道的相互作用。我们假设离子通道的混杂性调节可能有助于治疗精神病和痴呆症的药物的疗效。
