V. N. Zhukov

Effect of destruction of the brain serotoninergic system on alcohol intake by rats in the early stages of experimental alcoholism

The study of the role of the serotoninergic system (SES) in the formation of alcohol addiction has not yet yielded unambiguous resul ts [8, 9], the reason evidently being that different species and s t ra ins of animals have been used for these purposes without regard to their different initial predisposit ion toward alcohol consumption [2]. Investigations conducted on ra t s predisposed and not predisposed to alcohol have revealed diffe rences in the serotonin (5-HT) content and response of the SES of the brain to administrat ion of a single dose of alcohol to animals of opposite groups [6, 7]. These resul ts shed some light on the problem but do not re veal the mechanisms of participation of the SES in the development of alcohol motivation.

Anesthetic properties of new amphiphilic mesidides

In order to broaden and extend the known concepts on the relationship between chemical structure and anesthetic activity, we synthesized a series of N-(w-substituted aminoalkanoyl)mesidines (la-e, lla, b, llla-e) with various lengths of the alkane chain and different amine residues (secondary or tertiary amino group, one or two basic nitrogen atoms, etc.). These compounds can be provisionally divided into three groups.

Synthesis and study of the influence of certain products of serotonin metabolism, β-carbolines and related compounds, on the voluntary consumption of alcohol in animals

It is suggested that certain natural serotonin metabolites [i], as well as their cyclic analogs, representing compounds of the group of 8-carbolines, may play a substantial role in processes of formation and manifestation of alcohol dependence, since they intervene in the regulation of alcohol consumption [2, 3], beingproducts of ~n u~uo cyclization of serotonin and its metabolites with acetaldehyde -a metabolite of ethanol [4]. The incorporation of these compounds into the mechanism of formation of alcohol dependence may be determined by their ability to intervene in certain neurochemical processes [4], in particular, the serotoninergic processes. Moreover, the high affinity for the benzodiazepine receptor [5] suggests possible intervention of the compounds under consideration in the emotional processes associated with the attraction to alcohol.

Synthesis and anesthetic activity of acetomesidides containing tropane and piperidine fragments

5. L. S. Kaminskii, Statistical Processing of Laboratory and Clinical Data [in Russian], Leningrad (1964), pp. 17-35. 6. Methodological Recommendations for the Experimental (Preclinical) Study of Nonsteroid Antiinflannnatory Pharmacological Agents [in Russian], Moscow (1983). 7. US Patent No. 4,623,662; RZh. Khim., No. 14050P (1987). 8. I. Litchfield and F. Wilcoxon, J. Pharm. Exp. Ther., 96, 99-113 (1949). 9. L. O. Randal and J. Selitto, Arch. Int. Pharmacodyn., iii, 409-419 (1957). I0. C. A. Winter, E. A. Risley, and G. W. Nuss, Proc. Soc. Exp. Biol. (NY), iii, 544-547 (1962).

Synthesis and pharmacological activity of tetrahydrobenzofuranol derivatives

It is a known fact that phenol compounds can inhibit the synthesis of prostaglandins by suppressing the activity of cyclooxygenase, and therefore may exhibit an analgesic effect, characteristic of nonnarcotic analgetics [i]. With this in mind, and in view of the fact that among the phenol compounds, 6-hydroxy-l,4-4a,gb-tetrahydrodibenzofuran comprises a structural fragment of morphine and some of its antagonists, we synthesized and studied the pharmacological properties of 7-aminomethyl-6-hydroxy-l,2,3,4-tetrahydrodibenzofurans (Ia-d) and 9-aminomethyl-8-hydroxy-l,2,3,4-tetrahydrodibenzofurans (IIa-c, e-g) in comparison with the analgetic effects of morphine and the opiate antagonist naloxone.

The Role of Catecholamines and Serotonin in the Formation and Maintenance of Susceptibility to Alcohol

No simple explanation has yet been offered of how the seroto-ninergic and noradrenergic systems function in alcohol dependence. Pharmacological studies on the involvement of these systems in the regulation of voluntary alcohol consumption have failed in this respect. Investigations of the effect of ethanol on the two systems, whether administered chronically or acutely, have given contradictory results, moreover. As described previously (Burov et al., 1981), we were able to sort cross-bred rats into those susceptible or not susceptible to alcohol, according to how long the effects of this narcotic were maintained. This enabled us to explore differences between the animal’s inborn characteristics, concentrating on metabolic, neurochemical, hormonal and behavioral systems.

Nitrogen-containing derivatives of pyrone-4-carboxylic acid

Compounds IIa-e give a blue color with iron chloride, in contrast to the acid I which gives a red color, and this enables the course of the reaction to be followed. Compounds IIa-e are amino acids and form salts with alkalis; the hydrochlorides are easily decomposed because the amino group is weakly basic: From dilute acid solutions of salts only the free bases can be obtained. An exception is the diaminocarboxylic acid betaine IIe which has a protonated nitrogen atom. In compounds IIa-e, the amino group is weakly basic because of conjugation between the amino group at C(6) and the carbonyl group of the pyrone ring.