Abstract

Myopia (nearsightedness) is a vision disorder with a blurring of far objects, affect millions worldwide. 7-methylxanthine (7-MX) is a molecule that is presently under clinical investigation for the treatment of myopia. In the present study, we have investigated sub-chronic and chronic toxicity of 7-MX in comparison to other clinically used methylxanthines i.e., caffeine and theobromine as per OECD guidelines 408 and 452. 7-MX was administered orally for 90 days at three different doses of 250, 500, and 1000 mg/kg for sub-chronic toxicity evaluation, and at a limit dose of 1000 mg/kg in 180 days chronic toxicity evaluation in rats. In sub-chronic treatment, 7-MX showed no mortality and signs for toxicity in any group, whereas 10% and 40% mortality with signs for toxicity were observed in caffeine and theobromine treated groups, respectively. A similar, safety profile was observed with 7-MX in 180 days of chronic toxicity study. Further, to confirm any morphological changes in organs; ultrasound and X-rays analysis were performed and no changes in the size of organs, cyst formation, fluid retention, or crystal formation was observed. Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia.

摘要

近视（近视）是一种视力障碍，远处物体模糊，影响全球数百万人。7-甲基黄嘌呤 (7-MX) 是一种目前正在临床研究中用于治疗近视的分子。在本研究中，我们根据 OECD 指南 408 和 452 研究了 7-MX 与其他临床使用的甲基黄嘌呤（即咖啡因和可可碱）相比的亚慢性和慢性毒性。7-MX 在三种不同的情况下口服给药 90 天亚慢性毒性评价的剂量分别为 250、500 和 1000 mg/kg，大鼠 180 天慢性毒性评价的极限剂量为 1000 mg/kg。在亚慢性治疗中，7-MX 在任何组中均未显示死亡率和毒性迹象，而在咖啡因和可可碱治疗组中分别观察到 10% 和 40% 的死亡率和毒性迹象。在 180 天的慢性毒性研究中，使用 7-MX 观察到了类似的安全性。此外，确认器官的任何形态变化；进行了超声和 X 射线分析，未观察到器官大小、囊肿形成、液体潴留或晶体形成的变化。因此，7-MX 180 天的重复剂量研究可能会增加临床使用 7-MX 安全有效治疗近视的可能性。