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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.
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 1979,
Radiobiologiia,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 1993,
Radiation research,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 2003,
Radiatsionnaia biologiia, radioecologiia,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 1979,
Radiobiologiia,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 2001,
Radiatsionnaia biologiia, radioecologiia,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 1999,
Biofizika,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 2013,
Radiatsionnaia biologiia, radioecologiia,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 1974,
Radiobiologiia,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
January 2012,
Journal of inorganic biochemistry,
M V Filimonova, and
L I Shevchenko, and
V M Makarchuk, and
E A Chesnakova, and
O S Izmest'eva, and
T S Korneeva, and
A S Filimonov
March 2018,
The Journal of biological chemistry,
