Filimonova M V, Shevchenko L I, Makarchuk V M, Chesnakova E A, Izmest'eva O S, Korneeva T S, Filimonov A S
Radiats Biol Radioecol. 2015 May-Jun;55(3):250-9.
The study of radioprotective activity of NO-synthase inhibitor, N-S-isothiourea derivative T1023 showed that this compound has a significant therapeutic range of radioprotective activity (5.5-6.0) and its optimal radioprotective dose is 1/4 LD16. The value of its Radiation Dose-Reduction Factor totaled 1.4-1.8. We have demonstrated a pronounced pharmacodynamic interaction of T1023 with some known radioprotectors. The character of the interaction was determined by its vasoactive properties. Combined use of T1023 and cystamine, which causes a decrease in vascular tone, was accompanied by a statistically significant weakening of the radioprotective effect. But, the combined use of T1023 with serotonergic and adrenergic radioprotectors having a pressor action caused a statistically significant increase in the radioprotective effect. Moreover, T1023 combined with such radioprotectors caused the synergistic radioprotective effect even when used at small doses that do not have any radioprotective effect alone. The findings suggest that NOS inhibitors can be effective radioprotectors and are able to create new opportunities for the development of safer radioprotective agents. The very same compound T1023, according to current criteria of pharmacological screening, is certainly promising for further investigations.
对一氧化氮合酶抑制剂N-S-异硫脲衍生物T1023的辐射防护活性研究表明，该化合物具有显著的辐射防护活性治疗范围（5.5 - 6.0），其最佳辐射防护剂量为1/4 LD16。其辐射剂量降低因子的值总计为1.4 - 1.8。我们已经证明T1023与一些已知的辐射防护剂存在明显的药效学相互作用。相互作用的性质由其血管活性特性决定。T1023与导致血管张力降低的胱胺联合使用时，辐射防护作用在统计学上显著减弱。但是，T1023与具有升压作用的血清素能和肾上腺素能辐射防护剂联合使用时，辐射防护作用在统计学上显著增强。此外，T1023与这类辐射防护剂联合使用时，即使以单独使用无任何辐射防护作用的小剂量使用，也会产生协同辐射防护作用。这些发现表明，一氧化氮合酶抑制剂可以成为有效的辐射防护剂，并能够为开发更安全的辐射防护剂创造新机会。根据当前药理学筛选标准，化合物T1023确实有进一步研究的前景。
