[EFFECT OF MEDIATOR-TYPE DRUGS ON HUMAN PSYCHOPHYSIOLOGICAL STATUS DURING MODEL OPERATOR ACTIVITY].

In a placebo-controlled study, changes in psychophysiological status of operators (38 healthy male volunteers aged 23-35 years) performing 4-hour model operator activity were evaluated after a single oral administration of typical representatives of the different classes of drugs (haloperidol, proroxan, yohimbine hydrochloride, propranolol, mesocarb, isoprenaline, Belladonna extract, anabasine hydrochloride, valproate sodium, and phenazepam), which are used for the treatment, rehabilitation and prophylaxis of common diseases. It was found that all the drugs modified to a greater or lesser extent some components of the model operator activity. Isoprenaline and phenazepam had the most negative effect on the psychophysiological indicators and quality of the modeled operator activity. The results should be considered before administration of such drugs to working operators.

[Effect of ladasten on reproduction function in male rats].

The effect of ladasten (bromantan) on the development of emotional stress and reproduction activity was studied in male rats. Ladasten administration led to restoration of the stress-violated orientational reactions and body weight, activation of the spermatogenesis (increase in the number and mobility of spermatozoas), normalization of the fertilizing capacity of spermatozoas, and reduction in the loss of embryos.

[Neurophysiological and psychopharmacological effects of eiconol--a complex of unsaturated fatty acids]. / Neirofiziologicheskie i psikhofiziologicheskie éffekty éikonola--kompleksa nepredel'nykh zhirnykh kislot.

The effect of omega-3 polyunsturated fatty acids on the psychophysiological state of an operator was studied and mechanisms of the drug action were analyzed based on the EEG data. Changes in the psychophysiological and hemodynamic characteristics, EEG, and catecholamine excretion after a 30-day administration of eiconol--a complex of unsaturated fatty acids--in a daily dose of 8 g were studied in a group of 16 middle-aged healthy male operators. It was established that eiconol decreases systolic arterial pressure, reduces adrenalin excretion with urine, imparts the sense of well-being, improves the parameters of activity and the attention stability and concentration, and decreases the level of static tremor. The drug reduces basic anxiety level and motivation to the operator performance, but at the expense of some decrease in the sensomotor coordination. By the pattern of EEG profile changes, including an increase in the theta (5-7 Hz) and beta (15-28 Hz) bands and a decrease in the delta (0.8-2.0 Hz) band, eiconol resembles psychotropic agents of the adrenoblocking and GABA-ergic types, especially benzodiazepine activators.

Toxic effect of single treatment with bromantane on neurological status of experimental animals.

Neurotoxicological profile of actoprotector bromantane was studied on rats using S. Irwin's protocol of multi-test observation. The drug in doses of 30-300 mg/kg stimulated and in doses of 600-9,600 mg/kg suppressed behavioral activity. Spontaneous motor activity increased after single treatment with bromantane in doses of 30-300 mg/kg, did not change after treatment in doses of 600 mg/kg, and was inhibited after treatment in doses above 600 mg/kg. In doses of 300-600 mg/kg the drug reduced pain sensitivity threshold and in doses above 600 mg/kg elevated the pain threshold and tactile sensitivity and reaction to knock. Bromantane induced mydriasis in all studied doses; in doses above 10 g/kg the preparation induced blepharoptosis. In doses above 5 g/kg bromantane slightly increased respiration rate and depth (Kussmaul-like respiration). In some animals bromantane in high doses induced regurgitation, diarrhea, and polyuria. Rectal temperature decreased by 0.5-1 degrees C after virtually all doses. Behavioral effects of bromantane in doses of 30 and 600 mg/kg were associated with stimulation of the central dopamine and suppression of muscarinic and nicotinic cholinergic structures, n-cholinolytic effects of bromantane was more pronounced at a dose of 30 mg/kg than at a dose of 600 mg/kg.

[Effect of tanakan on psychophysiological status of patients with asthenic disorders]. / Vliianie tanakana na psikhofiziologicheskoe sostoianie bol'nykh s astenicheskimi rasstroistvami.

A clinical pharmacological 56-day trial was devoted to the effect of tanakan on the psychophysiological state of 26 patients with psychogenic and post-traumatic asthenic disorders. The drug was found to produce a positive effect on the psychophysiological state, with most pronounced improvement in the attention characteristics, short-term visual memory, operational component, and integral operator performance index. The results confirmed the positive action of tanakan on the cognitive and mnestic functions, which is analogous to the effect of nootropes. The antiasthenic, anxiolytic, antiamnesic, and vegetotropic components in the pharmacological spectrum of tanakan correlate with the positive psychophysiological effects. It is shown that positive changes in the psychophysiological state play an important role in the complex therapeutic action of tanakan in the treatment of asthenic disorders.

[Operator activity and changes in the functional state of central adrenergic systems (a neurophysiological study)]. / Operatorskaia deiatel'nost' pri izmeneniiakh funktsional'nogo sostoianiia tsentral'nykh adrenergicheskikh sistem (neirofiziologicheskoe issledovanie).

With a view to increasing the quality of prognosis of the effect of central adrenergic drugs upon the operator psychophysiological state and performance, we studied correlations between changes in the psychophysiological performance parameters and the spectral-coherent EEG characteristics in a group of 20 healthy volunteers after moderate enhancement or reduction of the central adrenergic system activity by yohimbine and pyrroxan. The two drugs produced a marked opposite influence (positive for yohimbine and negative for pyrroxan) upon the visual memory, attention, and visual signal analysis, which was correlated with opposing changes in the EEG characteristics, predominantly in the right hemisphere. This result must be taken into account in determining indications and co-unterindications for the particular drug administration to working operators.

[Effect of gidazepam on the motivational component of operator activity]. / Vliianie gidazepama na motivatsionnye komponenty operatorskoi deiatel'nosti.

It is demonstrated that the system of forming motivation to achieve high results and the system of realizing this motivation during the operator activity are independently affected by the psychotropic agent gidazepam.

[Effect of bromantane on the rat neurologic status in two month course]. / Vliianie bromantana na nevrologicheskii status krys pri dvukhmesiachnom vvedenii.

The oral administration of bromantan for two months on a toxic dose level produced a sex-dependent psychodysleptic action upon rats: the effective (30 mg/kg), intermediate (150 mg/kg), and toxic (600 mg/kg) doses reduced the motor activity in males, while not affecting (or increasing) this activity in females. The effective dose stimulated, and the toxic dose suppressed, the research activity and increased the number of grooming episodes, while ambiguously influencing the emotional state of rats. In the initial stage of treatment, bromantan causes hypothermia; in the second month, this effect is replaced by slight hyperthermia. Prolonged administration of a large dose of bromantan oppressed food uptake and slightly increased drink uptake. Upon the bromantan treatment, the body weight increased in females and decreased in males. The bromantan treatment course increased the muscle strength of rats; the operant activity was optimized during the first month of the course. The general physiological and behavioral characteristics of animals restored within two months after termination of the treatment course. During this period, the test animals exhibited no significant behavioral symptoms indicative of the drug dependence. The two-month treatment did not lead to the development of tolerance with respect to the optimizing drug action upon the physical and operant capacity.

[The neuro- and psychophysiological effects of bromantane]. / Neiro- i psikhofiziologicheskie éffekty bromantana.

The study of EEG and psychophysiological parameters and their correlations in 10 healthy volunteers after single oral administration of bromantan in comparison with placebo revealed favourable influence of the drug on operators' functional state. By EEG-profile (increase in middle-frequency alpha-rhythm power with lowering of powers in delta- and beta1-bands) bromantan is similar to many drugs with moderate psychostimulating, antiamnestic and antihypoxic properties. Bromantan does not alter the subjective state and principal components of operators' performance in untired men but promotes the appearance of EEG-signs of moderate vigilance rise and forming of productive action state coupled with favourable for precise motor performance tremor reduction. Operator's functional state optimization leads to extension of reserve abilities and probably causes efficiency of bromantan as a well known remedy for maintenance of high working capacity in tired operators and under extreme conditions.

[Effects of bromantane and sidnocarb on long-term operant conditioning and its vegetative correlates in rats]. / Vliianie bromantana i sidnokarba na éffektivnost' dlitel'noi operantnoi deiatel'nosti i ee vegetativnye korreliaty u krys.

Bromantan (20 mg/kg, p.o.) and sydnocarb (10 mg/kg, p.o.) augment the efficacy of a 5-h operant activity in rats, the effect being achieved through different pathways. Sydnocarb increases the number of operant reactions and exhausts the sympathico adrenal system reserves. Bromantan favors the activity optimization by reducing the number of errors at a smaller number of operant reactions. Bromantan increases the tension of motivational component (electric pain irritation avoidance), whereas sydnocarb decreases this component of the operant behavior. None of the two drugs affects the degree of functional activation of the cardiovascular system.

[Effect of the long term administration of bromantan on the reproductive function in rats]. / Vliianie bromantana pri kursovom vvedenii na reproduktivnuiu funktsiiu krys.

Bromantan is a new psychostimulator possessing actoprotector properties. The drug was administered to rats over two months (males) and two weeks (females) at a daily dose of 30 and 200-mg/kg, and the reproduction function parameters were monitored. Then the experimental animals were coupled and the embryonal characteristics of the breed were determined. Upon termination of the drug administration, the functional state of sperm and the morphology of gonads were studied again. It was found that bromantan (30 mg/kg) unreliably decreases the absolute amount of sperm in males. In females, the drug did not affect the ovary weight coefficient and increased the gestation index. After termination of the drug administration, the ovary weight coefficient increased. Bromantan affected neither the fertilizing capacity of male and female gametes nor the embryonal characteristics of the breed.

[The effect of bromantane on the cardiovascular and sympathetic-adrenal systems in animals]. / Vliianie bromantana na serdechno-sosudistuiu i simpatiko-adrenalovuiu sistemu zhivotnykh.

Bromantan administration markedly increases the stroke and minute blood volume at a reduced heart rate and peripheral resistance in anaesthetized rats, while the systemic arterial pressure exhibits an insignificant short-time increase. Bromantan also weakly increases the pressor effects of adrenaline and noradrenaline. In anaesthetized cats, bromantan modifies the shape of the amplitude-frequency characteristic of EEG measured in the upper cervical ganglion, reducing (against the initial level) the induced potential in the frequency range of the preganglionic fiber stimulation (1-10 and 25-30 Hz). In freely moving rats, capable of well-learnt Sidman's [correction of Seedman's] operant activity, bromantan showed a reliable tendency to decrease the rate of noradrenaline and adrenaline excretion with urine.

[The effect of bromantane on the erythro- and leukocytic profile of the peripheral blood in rats]. / Vliianie bromantana na éritro- i leikotsitarnyi profil' perifericheskoi krovi.

The specific effect of bromantan on blood tissue is demonstrated in rats. In chronic injection in a dose of 30 mg/kg bromantan raised the level of hemoglobin and leukocytes. In doses of 150 and 600 mg/kg it increased at first (3 months) and then reduced the level of erythrocytes, hemoglobin, and leukocytes. Reversible poikilocytosis, granulocytosis, and agranulocytosis were encountered. Hyperchromatosis and hypertrophy of the hepatocytes were found in the tissues of the liver and hemosiderosis was discovered in the spleen. It is suggested that the blood tissue is a "target" in the toxic effect of bromantan.

[The characteristics of the neuropsychotropic activity of bromantane in laboratory animals]. / Kharakteristika neiropsikhotropnoi aktivnosti bromantana u laboratornykh zhivotnykh.

Bromantan [N-2-(para-(bromphenyl)-N-2-(aminoadamantan)] possesses psychostimulating activity in experiments on animals. With LD50 8100 mg/kg (mice, intraperitoneal injection) activates simple and complicated forms of behavior, induces EEG effects typical of psychostimulators, is an antagonist of substances with a deprivationg neuropsychotropic effect. Bromantan is characterized by a positive effect on mnemonic processes and on obtaining the results of complex operant activity in rats.

[Adamantane derivatives enhancing body's resistance to emergencies]. / Proizvodnye adamantana, povyshaiushchie ustoichivost' organizma k ékstremal'nym vozdeistviiam.

A total of 329 novel adamantane derivatives have been synthesized and pharmacologically studied. Among them, the compounds containing halogen-containing aromatic radicals in the second position show the most pronounced effect on animal resistance to the emergencies induced by its habitat and performance. N-(2-adamantyl)-N-(para-bromphenyl)amine (bromantane) possesses a low toxicity, a high ability to enhance the physical and operant working maintenance of animals, to accelerate its recovery in developed fatigue, in hyperthermia and hypoxia in particular. 2-(para-chlorobenzoylamine)adamantane (chlodantane) has the processes of a rapid-action adaptogenic agent by enhancing the resistance of animals to various physical and toxically chemical noxious agents. The two compounds have immunostimulating effects in secondary stress-induced immunodeficiencies whose mechanism of action is a membranous protective activity.

[The mechanisms of the neurotropic action of bromantan]. / Mekhanizmy neirotropnogo deistviia bromantana.

The main components of bromantan central neurotropic effect is its dopamine-positive activity: antagonism (5 mg/kg) to the effects of neuroleptics in rats, blocking (50 microM) of dopamine synaptosomal capture, and a complicated in structure influence on the serotoninergic mediator systems--inhibition of neuronal capture of serotonin (50 microM), behavior responses to 5-hydroxytryptophan (1-20 mg/kg) in mice, decrease in the mediator content in intact rat brain when administered in doses lower than 5 mg/kg, and the absence of this parameter with the use of higher doses. The central noradrenergic effect of the drug is less expressed: blocking of the synaptosomal capture of norepinephrine in higher (more than 500 microM) concentrations), and absence of an effect, in distinction from sydnocarb, 1-5 mg/kg, on the mediator content in intact rat brain. The drug (1-50 mg/kg, intravenously) has no effect on neuro-muscular transmission in cats and in higher doses (30-600 mg/kg) inhibits to a certain degree the central effects of nicotine and arecoline.

[The effect of the actoprotector preparation bromantane on the postnatal development of rat pups]. / Vliianie akroprotektornogo preparata bromantan na postnatal'noe razvitie krysiat.

The purpose of this work was study of the late-term results of a course of the actoprotector bromantan on the formation and development of the rat progeny. Bromantan was given per os daily in doses of 30, 150, and 600 mg/kg once a day: females received the drug for 15 days (2.5 estrous cycles), males for 60 days (whole cycle of spermatogenesis). When the course of treatment with the drug ended, the females were put together with the males for two weeks. The experiments were subdivided into two series: in series I the progeny obtained from coupling of experimental males with intact females was studied, in series II the progeny of intact males and experimental females. According to the results of the investigation, bromantan produced a late-term effect on the formation and development of the offsprings. The number of females who gave birth in series I and II of the experiment, despite a low dose-dependent increase, did not differ significantly from the controls. In series I of the experiment the litter increased insignificantly depending on the dose (by 0.3, 14.9, and 23.4%, respectively). In distinction, in the case of experimental females given 30 and 600 mg/kg bromantan before copulation (series II) the number of young rats in the litter insignificantly reduced (by 34.9 and 44.2%), in the case of rats given 150 mg/kg bromantan the litter increased (by 45%, p < 0.05). Both in series I and series II the mean weight of the newborns in the first week was significantly higher than the weight of the controls. After that the growth in body weight was insignificantly slower. Evaluation of the functional condition of the nervous system and terms of physical development of the progeny in series I and II of copulation showed an insignificant increase in the rate of maturation of the sensorimotor reflexes and physical parameters of the young experimental rats. The "open-field" test conducted on the 40th day of life showed increase of motor (by 8.0-21.6%) and exploration activity (by 94.5-109.9%, p < 0.05) in the young experimental rats of series I and, at the same time, decrease of the grooming parameters (by 26.9-63.5%, p < 0.05) and emotionality. In all experimental groups of series II horizontal and vertical motor and searching activity was reduced. The authors believe that the actoprotector bromantan, possessing a dopaminergic effect in the mechanism of its action, may cause a late-term influence on prolactin secretion in lactating rats. The deficiency in this hormone in the early period of postnatal development affects the neurochemical organization of the hypothalamo-hypophyseal region and the brain areas connected with it, involving in this case also the mechanisms of sexual differentiation of the brain and, as a consequence, the somatic and sexual development of the progeny.

[The effect of gidazepam on the activity of the sympatho-adrenal system in operators working under the usual and complicated conditions]. / Vliianie gidazepama na aktivnost' simpato-adrenalovoi sistemy u operatorov pri rabote v obychnykh i oslozhnennykh usloviiakh.

In healthy volunteers a single dose (0.05 g) of hydazepam does not change, but in subjects with psychogenic stress-reactions one-week course of the drug (0.05 g/24 h) intensifies to optimum activation of the sympathoadrenal system in response to standard operator load, inducing prevalent excretion of norepinephrine but not of epinephrine in the urine and maintains a high level of dopamine and DOPA excretion. In operators working in a state of hypercapnia and hyperthermia a single dose of hydazepam (0.05 g) blocks stress activation of the sympathoadrenal system. In a state of hyperthermia hydazepam normalizes the blood histamine and serotonin content. In all cases hydazepam improves the condition of the operators and the quality of their work, which allows it to be considered an effective and safe agent for the correction of stress-induced disorders in operators.

[The effect of gidazepam on the cardiovascular system function in patients with neurotic reactions and in healthy subjects under aggravated conditions]. / Vliianie gidazepama na funktsional'noe sostoianie serdechno-sosudistoi sistemy bol'nykh s nevroticheskimi reaktsiiami i u zdorovykh lits v oslozhnennykh usloviiakh.

Administration of 0.05 g gidazepam once or twice daily for 7 days increased the stroke volume (SV) and circulation volume (CV) and reduced total peripheral resistance in neurotic patients. In healthy individuals 0.05 g gidazepam administered 60 min before an important examination stabilized CV. In subjects kept for 60 min in a microclimate with increasing temperature (55 +/- 2 degrees C, relative humidity 75-80%, rate of movement 1.5 m/min, rectal temperature at the end of exposure 39 degrees C) 0.05 g gidazepam administered 60 min before overheating optimally reorganized the reaction of the cardiovascular system, stabilized the SV at the initial level, which together with the growing heart rate increased the CV and provided sufficient perfusion of the vital organs. In healthy subjects working as operators for 4 h under conditions of hypercapnia (1.5% CO2), a single administration of 0.05 g gidazepam one hour before the beginning of work reduced the pulse pressure and increased the SV. The results obtained are evidence of the safety of using gidazepam as a corrector of emotion-induced disorders in operator performance under extreme conditions.