Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
Department of Pathology, Augusta University, Augusta, GA, USA.
Drug Chem Toxicol. 2022 May;45(3):1383-1394. doi: 10.1080/01480545.2020.1833904. Epub 2020 Oct 19.
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.
近视(远视)是一种视力障碍,表现为远处物体模糊不清,影响了全球数百万人。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 以 250、500 和 1000mg/kg 的三个不同剂量进行口服给药 90 天,用于亚慢性毒性评估,在 180 天的慢性毒性评估中以 1000mg/kg 的限量剂量在大鼠中进行。在亚慢性治疗中,7-MX 没有显示出任何死亡率和毒性迹象,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,7-MX 也观察到了类似的安全性概况。此外,为了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 的 180 天重复剂量研究可能增加了将 7-MX 临床用于安全有效治疗近视的可能性。