Combined effects of antiorthostatic suspension and ionizing radiation on the behaviour and neurotransmitters changes in different brain structures of rats.

Space flight factors (SFF) significantly affect the operating activity of astronauts during deep space missions. In contrast to an orbital flight, leaving the Earth's magnetic field is fraught with the dangers of exposure to ionizing radiation and more specifically, the high-energy nuclei component of galactic cosmic rays. Microgravity, just another critical non-radiation factor, significantly affects the normal functioning of the CNS. Some morphological structures of the brain, such as the prefrontal cortex and the hippocampus, that are rich in monoaminergic and acetylcholinergic neurones, are the most sensitive to the effects of ionizing radiation and non-radiation spaceflight factors (SFF). In this work we have studied the combined effects of microgravity (in antiorthostatic suspension model, AS) and irradiation (γ-ray and protons in spread-out Bragg peak) on the behaviour, cognitive abilities, and metabolism of monoamines and acetylcholine in the key structures of the rat's brain. Irradiation (as independently as combined with AS) resulted in the decrease of thigmotaxis in rats. Learning problems, caused by the malfunctioning of the working memory but not the spatial memory, were observed in response to AS as well as to the SFF in combination. Analysis of monoamines metabolism showed that the serotoninergic system was the most affected by the SFF. Concentration of acetylcholine in the hippocampus significantly increased in the groups of irradiated rats, and in the groups which were exposed to the SFF in combination, compared to the rats exposed only to AS.

Assessment of the classification abilities of the CNS multi-parametric optimization approach by the method of logistic regression.

Assessment of "CNS drugs/CNS candidates" classification abilities of the multi-parametric optimization (CNS MPO) approach was performed by logistic regression. It was found that the five out of the six separately used physical-chemical properties (topological polar surface area, number of hydrogen-bonded donor atoms, basicity, lipophilicity of compound in neutral form and at pH = 7.4) provided accuracy of recognition below 60%. Only the descriptor of molecular weight (MW) could correctly classify two-thirds of the studied compounds. Aggregation of all six properties in the MPOscore did not improve the classification, which was worse than the classification using only MW. The results of our study demonstrate the imperfection of the CNS MPO approach; in its current form it is not very useful for computer design of new, effective CNS drugs.

[Nonsteroidal anti-inflammatory drugs. Declaration I. A study of interrelation "structure--the effectiveness of anti-inflammatory action"].

Using the computer system SARD-21 (Structure Activity Relationship & Design) the structural features typical for high- and low- effective nonsteroid anti-inflammatory drugs (NSAIDs) were analyzed. This information has been used for the model for prediction of anti-inflammatory effectiveness of medicines with 76% and 81% level of recognition by two methods. New data can be used for creating new highly effective NSAIDs, and for increasing effectiveness of already known components.