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To discover new cognition enhancers, a set of virtually designed synthesizable compounds from different chemical series was investigated using two computer-aided approaches. One of the approaches is prediction of biological activity spectra for substances (PASS) and the second is prediction of toxicity, mutagenicity, and carcinogenicity (DEREK). To increase the probability of finding new chemical entities, we investigated a heterogeneous set of highly diverse chemicals including different types of heterocycles: five-membered (thiophenes, thiazoles, imidazoles, oxazoles, pyrroles), six-membered (pyridines, pyrimidines), seven-membered (diazepines, triazepines), fused five+six-membered heterocycles (indoles, benzothiazoles, purines, indolizines, neutral, mesoionic, and cationic azolopyridines). A database including 5494 structures of compounds was created. On the basis of the PASS and DEREK prediction results, eight compounds with the highest probability of cognition-enhancing effect were selected. The cognition-enhancing activity testing showed that all of the selected compounds had a pronounced antiamnesic effect and were found to reduce significantly scopolamine-induced amnesia of passive avoidance reflex (PAR). The action of compounds at doses of 1 and 10 mg/kg caused a statistically significant increase in latent time of reflex and in the number of animals, which did not enter the dark chamber when testing the PAR. Therefore, on the basis of computer prediction, new cognition-enhancing agents were discovered within the chemical series, in which this activity was not known previously.

The study of novel selective anxiolytic afobazol on rats with experimental intracerebral post-traumatic hematoma (cerebral hemorrhage) demonstrated its efficiency in a dose of 5 mg/kg applied by a single or repeated administration for 2 weeks. The preparation significantly decreased the incidence of neurological disturbances in most rats (pareses, paralyses, convulsive movements, lateral posture). The therapeutic course of afobazol improved survival rate. Afobazol improved learning and memory in rats with cerebral hemorrhage in the conditioned passive avoidance test and positively affected motor activity in the open field test, which was documented by significant increase in total motor activity indices. The effects of afobazol were more pronounced after course treatment. . Address for correspon dence: i_galaeva@mail.ru. I. P. Galaeva Disturbances of cerebral circulation, ischemic strokes and cerebral hemorrhages (CH) belong to leading factors of mortality. The consequences of stroke lead to disablement due to neurological deficiency and disturbances of mnestic and mental functions [3,10]. The most dangerous and resistant to treatment cerebral lesions in CH are caused by blood penetration into adjacent cerebral tissues during intracerebral hemorrhages, hemorrhages into the cerebral ventricles, subarachnoid space, extradural and subdural areas because of pronounced anatomic and physiological shifts, metabolic disturbances (including energy and substrate deficiency) ionic imbalance, glutamate excitotoxicity, oxidative stress, disturbances of enzyme functions, anoxic depolarization of the membranes and the death of neurons [3,8,9].Complex mechanisms of stroke pathogenesis necessitate the development of adequate pharmacotherapeutic methods aimed at restoration of cell homeostasis.To this end, a novel selective anxiolytic afobazol was synthesized at V. V. Zakusov State Research Institute of Pharmacology [6].The mechanism of its action is based on restoration of disturbed functions of GABA A -benzodiazepine receptor complex [6].Afobazol possesses antiradical potency, prevents ischemia-induced intensification of NO production in the brain [7], and exhibits protective properties in simulated glutamate toxicity in vitro. These data corroborate indications on the common links in the mechanisms of anxiogenesis and stroke pathogenesis, and explain importance to study the neuroprotective properties of afobazol.In this paper, we examined the effects of afobazol on survival rate and CNS function in rats with intracerebral post-traumatic hematoma. MATERIALS AND METHODSExperiments were carried out on random-bred albino male rats weighing 200-250 g. The rats were

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