S. A. Borisenko

Effect of a single injection of ethanol on permeability of the blood-brain barrier for14C-tyrosine,14C-dopa, and horseradish peroxidase

: Interleukin 2 used in vitro and in vivo induces effectively the recovery of cytotoxic activity of natural killers and lectin-dependent cellular cytotoxicity effectors in stress-immobilized CBA mice. This lymphokin can be used for correction of stressor depression in the cells of the natural anti-tumor resistance system.p. 145. 6. E. M. Gankina, N. A. Avdulov, and N. I. Maisov, Farmakol. Toksikol., No. 6, 17 (1982). 7. V. A. Zagorevskii, in: Physiologically Active Substances and Medicine [in Russian], Erevan (1982), p. 115. 8. G. N. Kryzhanovskii, A. A. Shandra, and L. S. Godlevskii, Farmakol. Toksikol., No. 6, 13 (1982). 9. I. P. Lapin, Farmakol. Toksikol., No. 6, 10 (1982). 10. K. S. Raevskii and N. I. Maisov, Byull. Eksp. Biol. Med., No. 6, 63 (1975). ii. C. Braestrup and M. Nielsen, in: Handbook of Psychopharmaoology, Vol. 17, New York (1983), p. 285. 12. C. Braestrup, T. Honore, M. Nielsen, et al., Biochem. Pharmacol., 33, 859 (1984). 13. R. J. Fanelli and J. O. McNamara, J. Pharmacol. Exp. Ther., 226, 147 (1983). 14. H. M~hler, Trends Pharmacol. Sci., ~, 116 (1981).

Effects of neurotropic drugs on hypothalamic self-stimulation

Amphetamine, cocaine, caffeine, morphine, and imipramine were shown to lower the threshold of the self-stimulation response at the hypothalamic level. Meprobamate, diazepam, and chlordiazepoxide have no effect on the threshold of self-stimulation but increase the number of self-stimulations in response to threshold, optimal, and above-optimal strengths of current. Benactyzine, DLK-25, and phenobarbital lower the threshold of self-stimulation and increase the number of self-stimulations to currents of all parameters. It is concluded that the drugs of the first group have a direct activating action on the system of positive emotions. Tranquilizers activate this system indirectly, through their depriming action on the system of negative emotions. Benactyzine, DLK-25, and phenobarbital activate the system of positive emotions and depress the system of negative emotions.

Microvascular permeability in rats predisposed and not predisposed to develop experimental alcoholism

Previous ~nvestigations [2] showed that ethanol, if injected intraperi toneally into ra t s predisposed to develop experimental alcoholism, enters the blood s t ream more slowly but is excreted from it more rapidly than in ra ts reject ing alcohol. It was suggested that these differences in the pharmacokinet ics of ethanol in animals of these groups were connected with differences in the functioning of their microc i rcula t ion and, in par t icular , differences in permeabi l i ty of the walls of the mic rovesse l s .

Permeability of the blood-brain barrier for [3H]-GABA in alcohol poisoning

Alcohol, especially chronic intake of alcohol, causes changes in the functional properties of the blood--brain barrier (BBB) and in the ability of various substances of exogenous and endogenous origin, such as lead, bismuth, acid dyes, albumin, mercury, phosphorus, sodium, iodine, etc., to penetrate into the brain (penetration is usually increased) [5]. In connection with the experimental study of the biological basis of alcoholism, the study of changes in the functional properties of the BBB and its permeability to endogenous substances which, in the modern view, may be involved in the mechanisms of formation of alcoholism, and in particular, for neurotransmitters, is particularly interesting. It has been shown that y-aminobutyric acid (GABA), considered to be the inhibitory mediator of the CNS, participates in the mechanism of the depressive effects of ethanol, and that functional insufficiency of the GABA system may be one cause of hyperexcitation during withdrawal [6, 9].

Development of tolerance to the activating action of morphine, amphetamine, and alcohol on the positive reinforcement system in rats

The development of cross tolerance to morphine, amphetamine and alcohol according to their activating effect on the system of positive reinforcement of the brain was shown on the basis of experimental self-stimulation reaction. It is assumed that the common neurophysiological and neurochemical mechanisms, particularly the adrenergic mechanisms of the system of positive reinforcement, lie at the basis of the development of tolerance to the drugs with euphoric type of action.

Effect of psychotropic drugs on capacity for mental and physical work in rats

Substances facilitating a self-stimulation response (amphetamine, cocaine, caffeine, morphine, benactyzine, phenobarbital, meprobamate, diazepam, chloridiazepoxide) and also electrical stimulation of systems of positive brain reinforcement, accelerate the development of ability of rats to pass through a maze. Amphetamine, cocaine, caffeine, morphine, benactyzine, phenobarbital, and electrical stimulation of the positive reinforcement systems increase the duration of forced swimming of the animals. Meprobamate, diazepam, and chlordiazepoxide have no effect on this parameter. It is postulated that the ability of psychotropic drugs to activate positive reinforcement systems is linked with their action on the capacity for mental and physical work.

Azacycloalkanes. XXXIII. Synthesis and antialcohol activity of α-alkylamino-γ-hydroxybutyric acid alkylamides

Previously we have demonstrated that the reactions of , -dihalogen-substituted valeric, caproic, and enanthic acids with amines offer a convenient pathway for the synthesis of -pyrrolidine[2], -piperidine[3], and ( -hexamethyleneimine)carboxylic acids [4]. In continuation of these investigations, we have studied the reactions of primary amines with , -dihalogenobutyric acids. It was found that the products of these reactions differ significantly from those obtained by aminolysis of the aforementioned , -dihalogenocarboxylic acids. In particular, no -azetidinecarboxylic acid is formed. Information important for understanding the laws of aminolysis of , -dihalogenobutyric acids was obtained from a comparative study of the rates of halogen ion formation during the aminolysis of -bromo-chlorobutyric acid (I) and the related model compounds ( -bromovaleric and -chloroenanthic acids) by an aqueous methylamine solution (see Table 1) [5 – 7]. As can be seen from the data presented in Table 1, the rates of bromine ion formation during the aminolysis of acid I and the model -bromovaleric acid are virtually the same, while the rates of chlorine ion formation during the aminolysis of acid I and the model -chloroenanthic acid differ by almost one order of magnitude. Previously [5] we demonstrated that a similar acceleration of the chlorine ion formation during the aminolysis of -bromo-chlorovaleric and -bromo-chlorocaproic acids is related to a more rapid cyclization of the intermediate -amino-chlorovaleric and -amino-chlorocaproic acids with the formation of pyrrolidine and piperidine cycles, respectively. In the case of aminolysis of the -bromo-chlorobutyric acid, the accelerated production of chlorine atoms related to the cyclization of -amino-chlorobutyric acid with the formation of an azetidine cycle is less probable. Indeed, comparative data [8] on the formation of 3-, 4-, 5-, 6-, and 7-member azacycloalkanes from the corresponding -bromoamines Br(CH2)nNH2 (n = 2 – 6) show that the rate of azetidine cycle formation is minimum and is about three orders of magnitude lower as compared to that for the piperidine cycle. A more probable explanation of the accelerated production of chlorine ions during the aminolysis of acid I can be based on a fast intramolecular attack of the -carbon atom by carboxylate anions II or III with the formation of intermediate products (substituted -butyrolactones IV or V) reacting with methylamine. The results of aminolysis of acid I by methylamine indicate that the reaction probably proceeds by the following scheme:

Effect of some drugs on ethanol-induced changes in bllod-brain barrier permeability for14C-tyrosine

This investigation seeks to compare the effects of membrane stabilizers chlorpromazine and alpha-tocopherol, and also the dopaminergic antagonist haloperidol, in changes in permeability of the blood-brain barrier for carbon 14-labelled tyrosine.

Psychophysiological and Genetic Factors Responsible for Alcohol and Morphine Dependence in Animals

Clinical observations and experimental findings leave no doubt as to the variety and profusion of alcohol’s and other narcotics’ effects on the organism. This explains why so many hypotheses have been produced explaining the development of alcoholism and drug addiction in terms of impairment of neurotransmitter regulatory systems (Anokhina, 1979; Tabakoff and Ritzman, 1979), of the characteristics of metabolism of xenobiotics (Belknap et al., 1972), of CNS sensitivity (Kakihana et al., 1966) or other contributory factors.