[The anxiolytic action of an analog of the endogenous peptide tuftsin on inbred mice with different phenotypes of the emotional stress reaction]. / Izuchenie protivotrevozhnogo deistviia analoga éndogennogo peptida taftsina na inbrednykh myshakh s razlichnym fenotipom émotsional'no-stressovoi reaktsii.

The anxiolytic effect of the synthetic analogue of the endogenous peptide tuftsin (Thr-Lys-Pro-Arg-Pro-Gly-Pro) was studied in inbred mice Balb/c (C) and C57B1/6 (B6) with different heritable types of emotional-stress reaction. In C strain with genetically high level of anxiety and "passive" type of behaviour under conditions of avoidable and unavoidable stress (open field, elevated plus-maze, light-dark chamber) the heptapeptide prevented manifestations of anxiety being administered intraperitoneally in a wide range of active doses (200-3000 mcg/kg). The drug did not change the behaviour of B6 mice with low level of anxiety and active type of emotional-stress reaction. The described effect is comparable with tranquilizing-activatory action of low doses of benzodiazepine tranquillizers, however, in contrast to the latter, the heptapeptide has no side inhibitory behavioural effects even in high doses. The heptapeptide may be considered as a promising new anxioselective drug without side inhibitory behavioural effects which are typical for benzodiazepine tranquillizers.

[A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)]. / Nootropnyi analog adrenokortikotropina 4-10-semaks (15-letnii opyt razrabotki i izucheniia).

Semax is one of the rare analogues of regulatory peptides which underwent all stages from fundamental investigations to practical usage. It has been demonstrated that this peptide is capable to stimulate operative memory and attention, to increase resistance to hypoxia and to improve brain circulation in experimental animals and human beings over prolonged period (20-24 h after intranasal administration in doses 0.015-0.050 mg/kg). Semax significantly improves memory and attention in healthy men under extreme conditions of activities. Moreover at present semax is successfully used in treatment of patients with different diseases of CNS. In the majority of cases the peptide exhibited positive effects and in no case it produced negative side actions or complications connected with its administration. There is good reason to believe that medical potentialities of semax have not been exhausted and in future new possibilities of its usage will be revealed.

[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. / Effektivnost' semaksa v ostrom periode polusharnogo ishemicheskogo insul'ta (klinicheskoe i élektrofiziologicheskoe issledovanie).

Efficiency of Semax (synthetic derivative of ACTH-4-10) was studied in 30 patients in acute period of hemispherical ischemic stroke. Control group consisted of 80 patients with the strokes analogous in severity and location of the damages and which were treated by conventional therapy. Different clinical rating scales were used for both objectivization of the severity of the patients' state and estimation of the degree of neurological defect. The control of Semax influence on the functional state of the brain included monitoring of EEG with mapping, repeated analysis of somatosensory evoked potentials and their mapping. It was established that including of Semax in combined intensive therapy of acute ischemic stroke had some influence on the rate of restoration of the damaged neurological functions in terms of increasing the regress of general cerebral and focal, especially motor disorders. The most effective daily doses were 12 mg for patients with strokes of moderate severity and 18 mg for patients with severe strokes (treatment course--5 and 10 days).

[The effect of beta-casomorphin-7 on the level of food and defense motivations in different types of learning]. / Vliianie beta-kazomorfina-7 na uroven' pishchevoi i oboronitel'noi motivatsii pri razlichnykh vidakh obucheniia.

The effects of intraperitoneal administration of the heptapeptide beta-casomorphin-7 (beta-C-7) on learning were investigated in white rats using T-maze, active and passive avoidance tests. The substance injected in the dose of 5 mg/kg 5 min prior to training accelerated the acquisition of food-reinforced task increasing the number of correct trials in T-maze. The same injection in the dose of 1 mg/kg impaired the acquisition of avoidance tasks. The heptapeptide didn't influence food motivation and consolidation of memory trace. The data obtained support the idea that beta-C-7 attenuated manifestations of defensive motivation.

[ANSA analysis. III. Synthesis of aminonaphthalinesulfonamide chromogenic substrates for protease analysis]. / ANSA-analiz. III. Sintez aminonaftalinsul'fonamidnykh khromogreenykh substratov dlia analiza proteaz.

A review of synthetic methods of peptide substrates containing aminonaphthalenesulphonamide (ANSA) as the detected leaving group is presented. Variations of aminoacylic and peptide ANSA derivatives using ANSA as the C-protect group at all stages of the peptide synthesis, condensations of the ANSA with the N-protected peptide fragment obtained preliminary, the application of aminoacyl-ANSA as syntones are discussed. The synthesis scheme used while determining optimal ANSA substrates that involves reactions of aminoacyl derivatives of aminonaphthalenesulfonylchlorides with amines is shown. The application of di-tert-butylpyrocarbonate, DCC, chlorodimethylformiminium chloride, alkylchloroformate as condensing agents is described. The protection of amino groups was carried out by using Boc- and Cbz- groups.

[The behavioral effects of beta-casomorphin-7 and its des-Tyr analogs]. / Povedencheskie éffekty beta-kazomorfina-7 i ego dez-Tyr-analogov.

The effects of intraperitoneal administration of the heptapeptide beta-casomorphin-7 (beta-K-7) and its des-Tyr analogues (beta-K-6 and beta-K-4) on spontaneous locomotor activity were investigated in rats using "Opto-Varimax", "RODEO-2" and "open field" tests. At 20 mg/kg 5 minutes prior to the beginning of measurements beta-K-7 produced a significant decrease in linear locomotion and rearing. As for beta-K-6 and beta-K-4, their influence on locomotion of the experimental animals was less evident. In contrast to beta-K-7, its des-Tyr analogues (20 mg/kg) produced a marked decrease in nose-poking behavior. Beta-K-7 in doses that had no effect on spontaneous behaviour (1 and 5 mg/kg) attenuated extreme behavioural displays under stress conditions. The experimental results suggest the advisability of further investigations of neurotropic properties of beta-K-7 and related peptides.

[Effects of systemically-administered beta-casomorphin-7 on nociception in rats]. / Deistvie beta-kazomorfina-7 na notsitseptsiiu krys pri sistemnom vvedenii.

The influence of food-derived heptapeptide beta-casomorphin-7 (beta-CM-7) on pain sensibility of white rats was studied by tail flick test. As shown for doses 10 and 20 mg/kg intraperitoneally, injected beta-CM-7 induced significant analgesia; lower peptide concentration (5 mg/kg) was ineffective. As a whole, there is a significant positive correlation between the intensity of analgesia and the quantity of administered exorphine. These changes of pain sensibility were observed for one hour after injection of heptapeptide; further measurements showed no significant difference of time reaction between control and experimental groups of rats. It was found out that animals with high native level of pain sensibility (4-8 sec) made the main contribution to manifestation of analgesia.

[Anticonvulsive properties of peptide ACTH4-7 pro-gly-pro detected in amygdaloid kindling and audiogenic epilepsy in rats]. / Protivosudorozhnie svoistva peptida AKTG4-7 pro-gli-pro, vyiavliaemye pri amigdaliarnoi raskachke i audiogennoi épilepsii u krys.

Effects of the ACTH4-7 pro-gly-pro, calcium valproate ("Germed", DDR) and nembutal on kindling preparation and audiogenic epilepsy were investigated. Development of after-discharges in response to repeated amygdaloid electrical stimulation was assessed in normal rats and in rats susceptible to audiogenic epilepsy (KM line of rats). ACTH4-7 pro-gly-pro had an anticonvulsant profile. ACTH4-7 pro-gly-pro decreased seizure threshold in the audiogenic epilepsy test, but did not prevent the motor convulsions.

[A possible approach to the analysis of protease mixtures]. / Vozmozhnyi podkhod k analizu smesei proteaz.

A problem of quantitative assay of proteases in complex mixtures is solved by using a set of peptide substrates with detectable (chromogenic or fluorogenic) groups (DGs). Quantitation of separate DGs released in reaction of enzyme mixture with a set of substrates is carried out in chromatographic analysis of reaction products. Reaction of peptide derivatives of aminonaphthalene sulfamides with a mixture of thrombin and proteases from viper venom shows the amounts of produced DGs to be proportional to the amounts of both thrombin and venom proteases, confirming the validity of proposed approach. There are cases of mutual influence of some components in proteases mixtures as illustrated by inhibition of trypsin activity in presence of viper venom; one determines enzyme activities in this specific mixture rather than their amounts.

[Effect an ACTH analog on the processes of learning and memory in rats]. / Vliianie analoga AKTG na protsessy obucheniia i pamiati u krys.

On the basis of the idea of the important role of neurotransmitter systems in realization of neuropeptide effects, the participation was studied of the monoaminergic systems in the mechanisms of the ACTH analogue influence on the processes of learning and memory in control animals and animals with a changed functional state of the monoaminergic systems. In parallel the influence was studied of the ACTH analogue on the content of the endogenic monoamines in various brain structures of rats. It has been shown that administration of the ACTH analogue in a dose of 10 mcg affects the elaboration and preservation of conditioned reflexes (CRs) of passive avoidance, CRs of two-side avoidance and labyrinth CRs only in conditions of changed functional state of the monoaminergic systems. Amnesia, usually elicited by 5-oxytryptophane and disulfiram is prevented by administration of the ACTH analogue. Administration of the ACTH analogue is accompanied by the intensification of serotonine metabolism in the midbrain and medulla and by an increase of noradrenaline content in the hypothlamus.