title: [Radioprotective Properties of NO-Synthase Inhibitor T1023: I. Indicators of Radioprotective Activity and Interaction with Other Radioprotectors].
abstract: 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.
authors: M V
authors: MV
authors: Filimonova
authors: L I
authors: LI
authors: Shevchenko
authors: V M
authors: VM
authors: Makarchuk
authors: E A
authors: EA
authors: Chesnakova
authors: O S
authors: OS
authors: Izmest'eva
authors: T S
authors: TS
authors: Korneeva
authors: A S
authors: AS
authors: Filimonov
mesh_terms: D000818:Animals; D003538:Cystamine / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000138:chemical synthesis; D005720:Gamma Rays; D006801:Humans; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental; D011835:Radiation Protection; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D004791:Enzyme Inhibitors; D011837:Radiation-Protective Agents; C000602057:T1023; D019001:Nitric Oxide Synthase; D013890:Thiourea; D003538:Cystamine