Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida , Tampa, Florida 33612, United States.
Mol Pharm. 2013 Dec 2;10(12):4728-38. doi: 10.1021/mp400571a. Epub 2013 Nov 18.
Current United States Food and Drug Administration (FDA)-approved lithium salts are plagued with a narrow therapeutic window. Recent attempts to find alternative drugs have identified new chemical entities, but lithium's polypharmacological mechanisms for treating neuropsychiatric disorders are highly debated and are not yet matched. Thus, re-engineering current lithium solid forms in order to optimize performance represents a low cost and low risk approach to the desired therapeutic outcome. In this contribution, we employed a crystal engineering strategy to synthesize the first ionic cocrystals (ICCs) of lithium salts with organic anions. We are unaware of any previous studies that have assessed the biological efficacy of any ICCs, and encouragingly we found that the new speciation did not negatively affect established bioactivities of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics compared to lithium carbonate. Indeed, the studies detailed herein represent an important advancement in a crystal engineering approach to a new generation of lithium therapeutics.
目前，美国食品和药物管理局 (FDA) 批准的锂盐存在治疗窗口狭窄的问题。最近寻找替代药物的尝试已经确定了新的化学实体，但锂在治疗神经精神疾病方面的多药理学机制仍存在争议，尚未得到匹配。因此，对现有锂固体形式进行重新设计以优化性能是一种低成本、低风险的方法，可以达到理想的治疗效果。在本研究中，我们采用晶体工程策略合成了锂盐与有机阴离子的第一个离子共晶（ICCs）。我们不知道以前有任何研究评估过任何 ICCs 的生物疗效，但令人鼓舞的是，我们发现新的物种形成并没有对锂的既定生物活性产生负面影响。我们还观察到，与碳酸锂相比，锂 ICCs 表现出调节的药代动力学。实际上，本文详细介绍的研究代表了一种新的晶体工程方法在新一代锂治疗药物方面的重要进展。
