A new class of substances exhibiting radioprotective and radiosensitizing effects depending on the concentration of the substance has been found. The radioprotective effect is probably due to the resonant absorption of radiation energy and its transformation into low-energy forms, as well as reactions with water radiolysis products. We studied the effects of 2,5-difeniloxazole and di[2-(5-feniloxazolil)]benzene in various concentrations in conjunction with irradiation on the growth of melanoma B-16 in mice and the average time of their lives. When using individual doses of irradiation and doses of preparations, we observed an increase in the average lifetime of mice and a reduced tumor size. These data allow us to conclude about the possibility of using these substances in the radiotherapy of tumors.

Исследован новый класс веществ, проявляющих радиозащитное и радиосенсибилизирующее действие в зависимости от их концентрации. Радиозащитный эффект обусловлен, вероятно, резонансным поглощением энергии излучения и переводом ее в низкоэнергетические формы, а также реакциями с продуктами радиолиза воды. Изучено влияние 2,5-дифенилоксазола и ди[2-(5-фенилоксазолил)]бензола в различных концентрациях совместно с облучением на рост меланомы В-16 у мышей и среднее время жизни животных-опухоленосителей. При облучении и введении исследуемых препаратов в отдельных дозах отмечено увеличение средней продолжительности жизни мышей-опухоленосителей и уменьшение размеров опухолей, что позволяет сделать заключение о перспективности применения изученных веществ в лучевой терапии.

At present, there are no simple and reliable methods for selection of compounds with physiological activity in super-low concentrations (SLC). The screening system with high predictability is proposed. At the beginning, experiment is carried out on infusorians--spirostoma. Their motion activity, behavior, living ability and shape are registered at concentrations of substances in a range of 10(-3)-10(-13) mol/l. If the effect is detected on spirostoma, then experiments are performed on laboratory animals or their isolated tissues. Specific deviations on injection substance in SLC are detected, depending on compounds class. Nine representatives of different classes of biologically active compounds are investigated in the work: carbofos, deltametrin, 3-quinuclidinyl benzylate, atropine, phenosan, fenazepam, dopamine receptor antagonist SCH-23390, ciprine, and hexenal. It is accepted that if compound action in SLC is observed on spirostoma, then effects in super-low doses are also detected in a whole animal.

Pentifin and dopamine D1 receptor antagonist SCH-23390 possess similar pharmacological properties. In the present work we studied in vitro effects of Pentifin on dopamine receptors. Experiments on rat ductus deferents showed that Pentifin acts as a weak ligand of dopamine receptors. Our results indicate that the antihaloperidol effect of Pentifin is not related to the blockade of dopamine receptors.

Experimental determination of the lifetimes of short-lived ligand – receptor complexes encounters considerable, frequently insurmountable difficulties because the conventional methods of “fast” kinetics widely used for the study of enzyme – substrate complexes are practically inapplicable to the interactions of active substances with receptors. This problem is mostly related to the complexity of the task of necessary purification of the receptor proteins. Additional difficulties are presented by a change in the complex-formation parameters of the receptors in the course of purification. Determination of the average lifetime of a complex formed between a ligand and a biological acceptor is useful in the following cases: (i) For predicting the duration of drug action. The lifetime of a complex between the drug and the biological target is, together with the rate of metabolism, one of the main factors determining the duration of the pharmacological action. (ii) For evaluating the lifetimes of short-lived (including intermediate) complexes formed in various stages of interaction between ligands and proteins. (iii) For selecting a proper method for separating bound and free labels in experiments employing radioligands. This time-consuming separation procedure is usually a “bottleneck” in the study of short-lived complexes. The process of a complex formation between a ligand and a biological acceptor can be described by the scheme