no -合成酶抑制剂T1023的辐射防护性能:I.辐射防护活性指标及其与其他辐射防护剂的相互作用

M V Filimonova, L I Shevchenko, V M Makarchuk, E A Chesnakova, O S Izmest'eva, T S Korneeva, A S Filimonov
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引用次数: 0

摘要

no合酶抑制剂n -s -异硫脲衍生物T1023的放射防护活性研究表明,该化合物具有显著的放射防护活性治疗范围(5.5 ~ 6.0),其最佳放射防护剂量为1/ 4ld16。其辐射剂量减值因子为1.4 ~ 1.8。我们已经证明了T1023与一些已知的放射性保护剂有明显的药效学相互作用。这种相互作用的性质是由其血管活性特性决定的。联合使用T1023和半胺会导致血管张力降低,并伴有统计学上显著的辐射防护效果减弱。但是,T1023与具有加压作用的血清素能和肾上腺素能放射保护剂联合使用,放射防护效果有统计学意义的显著增加。此外,T1023与这些放射防护剂联合使用时,即使单独使用不产生任何放射防护效果的小剂量也会产生协同辐射防护效果。研究结果表明,NOS抑制剂可以是有效的辐射保护剂,并能够为开发更安全的辐射保护剂创造新的机会。同样的化合物T1023,根据目前的药理学筛选标准,肯定有进一步研究的希望。
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[Radioprotective Properties of NO-Synthase Inhibitor T1023: I. Indicators of Radioprotective Activity and Interaction with Other Radioprotectors].

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.

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