Means for reducing alcohol motivation
(57) Abstract:The invention relates to medicine, pharmacology, and relates to means for reducing the consumption of ethyl alcohol and the severity of the pathological craving for ethanol. Apply m-chlorobenzylamino formula
< / BR>as a means of reducing alcohol motivation. The tool expands the Arsenal of tools specified destination. 2 Il., 3 table. The invention relates to the field of medicine, pharmacology, and relates to means for reducing the consumption of ethyl alcohol and the severity of the pathological craving for ethanol.Known medical use for this purpose teturama (disulfiram, antabuse), metronidazole, calcium carbimide [Burov Y. C., 1982, 1985], decoction of moss of baranca [Mashkovsky M. D., 1993], carbamazepine, fluoxetine [Daoust et al., 1992], ondansetron [Tomkins, Sellers, 1992].The main drawback of funds aversive therapy of pathological craving for alcohol (teturam, metronidazole, furunculosis barantsa) is that they all have the properties of a true therapeutic agents. Their protivoallergennoy effect is caused mainly by the secretion of negative conditioned reflex to alcohol. In the absence of pooe the condition of the success of this therapy. In addition, an integral part of teturama (and other related tools) are heavy vegetative disorders and complex painful sensations. All this is very poorly tolerated. There is also a wide range of medical contraindications to the use of the above medicines [Burov Y. C.,1982, 1985]. It is assumed that when alcoholism is an effective anticonvulsant drugs, possessing, in addition, anxiolytic, sedative, antidepressant, replacement anxiolytic effects of ethanol. Anticonvulsant carbamazepine (tegretol, Finlepsin) and antidepressant-inhibitor serotonin reuptake fluoxetine (prozac) is only effective in cases of alcoholism, due to masked depression. In addition, significantly reducing the consumption of alcohol in the experiment, these drugs in the clinic give unstable and much less pronounced effect.A new technical result is an expansion of the means used in the pharmacotherapy of alcoholism, reach use m-chlorobenzylidene (m-hbgm) as a means of reducing alcohol motivation.M - chlorobenzylamino formula
< / BR>is work in alcohol, isopropanol, easily soluble in organic solvents (chloroform, ether, hexane) [Agarkova B. N., 1974].Pharmacological properties of m-chlorobenzylidene. It is shown that m-chlorobenzylamino combines high anticonvulsant activity in the maximal electroshock, Karasyova, strychnine, camphor cramps with very low toxicity [Agarkova B. N., 1974]. Some indicators of the specific activity and the breadth of therapeutic action of the drug is superior to phenobarbital, phenytoin, benzonal. M-chlorobenzylamino at a dose of 100 mg/kg has a dampening effect on spontaneous bioelectric activity of the cerebral cortex of rabbits and reduces the lability of the nerve cells of the cortex. M - chlorobenzylamino not significantly alter locomotor activity and estimated responses in mice, has a slight muscle relaxant action, slightly increases the threshold electrobios sensitivity, significantly prolongs barbaray sleep, without affecting the period of sleep in mice. The drug also has a pronounced antiarrhythmic effect [Fateyeva S. N., 1983]. The mechanism of action of m-chlorobenzylidene not well understood. The detected potential of the cell and membrane permeability [Augerville Z. Z., 1981]. Experimentally it is shown that m-chlorobenzylamino with the introduction of the animal at anticonvulsant doses, changes the energy supply of the brain and limits the development of convulsive seizure [Khazanov C. A., 1986]. In addition, m-chlorobenzylamino shows garmentindustry activity against detoxifying liver enzymes - cytochrome P-450 enzyme conjugation of xenobiotics [Navajeevan Etc., 1984]. Found to have low acute and chronic toxicity m-chlorobenzylidene for laboratory animals. The drug has no teratogenic, mutagenic, allergogennym and immunotoxic effects.RESEARCH METHODS
The availability of new properties is confirmed by experimental studies. The experiments were conducted on rats male Wistar rats with an initial weight 140-150, Group of animals was subjected to initial testing for preference under conditions of free choice between a 15% solution of ethanol and water for 14 days. Each animal was kept in a separate cage placed on the cover two buradaki, one of which contained 15% solution of ethanol, and the second water. The amount of fluid you drink were recorded in ml per day in both buraidah; free flowing liquid is ve groups: rats, rejecting the ethanol - enrolled animals, consumption of ethanol which was less than 10% of the total amount consumed per day, and rats, preferring ethanol - enrolled in rats, consumption of ethanol which was more than 50% of the total number consumed per day fluid (megapixie rats). Animals, rejecting ethanol, in the experiment is not used. Animals, who preferred ethanol, broke into groups, which varied according to some experimental conditions: 1-I group for 10 months was maintained by force of alcoholism (animals received a 15% solution of ethanol as the sole source of liquid); group 2 animals were kept without access to ethanol.Then they were re-test within 14 days on the preference of ethanol under conditions of free choice, was isolated in a separate group of animals who changed their preference. The remaining rats were divided into two equal groups. First, starting from the 15th day, introduced m-chlorobenzylamino intragastrically at a dose of 100 mg/kg by the probe and recorded the average daily ethanol consumption in milliliters of 15% solution of ethanol, followed Peres the tats were calculated using t-student test.As a result of screening were allocated to 3 groups of animals: 1) rats than in ethanol at initial testing (so-called "megaplume animals) and have not replaced the preference as a result of chronic alcoholism; 2) rats, who preferred ethanol (the so-called "Malouda animals) contained without access to ethanol, have not replaced the preference; 3) rats than in water.The infusion of m-chlorobenzylidene were found to decrease alcohol consumption in animals 1-St and 2-nd group (table. 1, 2; Fig. 1, 2). The most pronounced and significant (p<0.01) decrease in alcohol consumption was observed in animals of the 1st group (table. 1; Fig. 1, 2). It decreased by 82.7% from baseline (14,01,93 ml of 15% solution of ethanol in the days before the introduction of m-chlorobenzylidene and 3,252,07 ml of the infusion of the drug). Animals of the 2nd group - 75% from baseline (12,232,21 ml and 5,102,42 ml, respectively) (table. 2; Fig. 1, 2). On alcohol consumption by rats prefer water, m-chlorobenzylamino had no effect (2,290,62 ml before administration of the drug and 1,890,47 ml background introduction) (table. 3; Fig. 1, 2). Reduction of alcohol consumption in rats occurred at 2-3 days of receiving m-chlorobenzylidene the tion.Thus, with the introduction of m-chloro-benzhydrylamine there is a substantial decrease in the consumption of ethanol in animals, long-term preferred ethanol water (Fig. 1, 2). They also noted the changing preferences of alcohol to water, i.e. under the influence of m-chlorobenzylidene change occurs alcoholic motivation. Therefore, discovered a new property of the m chlorobenzenamine, allowing you to use it as a means of reducing the consumption of ethyl alcohol and the severity of pathological attraction to him.Literature
1. Agarkova B. N. Anticonvulsant activity and electroencephalographic analysis of Central action of some derivatives benzhydrylamine. - Abstract. Diss. Kida. Biol. Sciences.-Tomsk, 1974.2. Augerville H. H. Anticonvulsant activity of some derivatives benzhydrylamine. - Abstract. Diss. Kida. Biol. Sciences. -Tomsk, 1981.3. Y. Boers Century Pharmacological agents for the treatment of alcoholism. - In the book: Pharmacology experimental alcoholism / edited by Y. C. Burova. M. , 1982, S. 7-28.4. Burov Y. C., N. Vedernikov.N. Neurochemistry and pharmacology of alcoholism. - M.: Medicine, 1985, S. 69-72.5. Mashkovsky M. D. Lekarstvennoyj funds - derivatives of urea on the system of microsomal oxidation in the liver. - Abstract. Diss. Kida. Biol. Sciences. - Tomsk, 1984.7. Khazanov Century A. the Effect of anticonvulsants phenobarbital, benzonal and galadima on the oxidation of succinate by the mitochondria of rat brain. - Abstract. Diss. ... candles. the honey. Sciences. - Tomsk, 1986.8. Fateyeva S. N. Antiarrhythmic action of some anticonvulsants. - Abstract. Diss. Kida. the honey. Sciences. Sverdlovsk, 1983.9. Daoust M - Les effets de la fluoxetine et de la tianeptine sur la consommation d alcool du rat dependant - Alcoologie, 1992, 14, 2, pp. 87-89.10. Tomkins D. M., Sellers E. M. - Effects of ondansetron on ethanol intake and behaviour - Alcoholism: Clin. Exp. Res., 1992, 16, 2, p. 368. The use of m-chlorobenzylidene formula
< / BR>as a means of reducing alcohol motivation.
where R1is hydrogen, fluorine or chlorine; R2is hydrogen or methyl, and pharmaceutical compositions based on
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new aminobenzophenones of the formula (I):
or their pharmaceutically acceptable salts. These compounds elicit properties of inhibitors of cytokines secretion, in particular, 1β-interleukin (IL-1β) and tumor necrosis α-factor (TNF-α) and to secretion of polymorphonuclear superoxide that are useful for treatment of inflammatory diseases, for example, skin diseases, such as psoriasis, atopic dermatitis. In the formula (I) R1 is taken among the group consisting of halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, cyano-group, carbamoyl, phenyl or nitro-group under condition that when R1 means a single substitute then it at ortho-position, and when R1 means more one substitute then at least one substitute of R1 is at ortho-position; R2 means one substitute at ortho-position being indicated substitute is taken among the group consisting of (C1-C3)-alkyl, (C1-C3)-alkoxy-group; R3 means hydrogen, halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, phenyl, cyano-, carboxy-group or carbamoyl; R4 means hydrogen atom or (C1-C3)-alkyl; Q means a bond or -SO2-; Y means (C1-C15)-alkyl, (C3-C10)-carbocyclic group or phenyl being each of them can be substituted optionally with one or some similar or different substitutes designated by the formula R5; R5 means halogen atom, (C1-C4)-alkyl, amino-, (C1-C3)-alkoxy-group, (C1-C3)-alkoxycarbonyl or -COOH; X means oxygen or sulfur atom. Also, invention relates to a pharmaceutical composition and to a method for treatment and/or prophylaxis of inflammatory diseases.
EFFECT: valuable medicinal properties of compounds and composition.
9 cl, 2 sch, 2 tbl, 29 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of N-desacetylthiocolchicine of the formula (I):
wherein n represents a whole number from 0 to 8; Y represents group CH2 or if n = 1 then can mean group NH also. These compounds elicit an anti-proliferative activity. Also, invention describes pharmaceutical composition based on compounds of the formula (I).
EFFECT: valuable medicinal properties of derivatives.
4 cl, 1 tbl, 4 ex
FIELD: veterinary medicine.
SUBSTANCE: method involves administering aqueous solution containing 4.5% of diamidine, in combination with 2.5% of primacine and 20% of polyethylene glycol-6000.
EFFECT: increased reliability of treatment results.
FIELD: medicine, neurooncology.
SUBSTANCE: one should carry out chemotherapy and irradiation till radical dosage. Moreover, 2-3 d before the onset of radiation therapy and during the whole course of irradiation one should indicate the intake of indometacin at daily dosage being 300 mg, and 8-14 d before the end of therapy course or the stage of radiation therapy it is necessary to conduct chemotherapeutic cycle with vincristine at total dosage being 4 mG and lomustine at total dosage 160-240 mg. At performing a split course of irradiation the intake of indometacin should be indicated between the stages. The innovation enables to increase radio sensitivity of malignant tumor, suppress angiogenesis, proliferative activity and increased cytotoxic activity of chemopreparations.
EFFECT: higher efficiency of therapy.
1 cl, 3 ex
FIELD: veterinary science.
SUBSTANCE: invention proposes preparation used in treatment and prophylaxis of bacterial-fungal infections in animals. The preparation comprises neomycin, furazolidone and dimethylolurea taken in the following ratio of components, wt.-%: neomycin, 1.2-1.5; furazolidone, 1.2-1.5, and dimethylolurea, the balance. Invention provides expanding spectrum of the preparation effect and enhanced effectiveness of its effect.
EFFECT: improved and valuable properties of preparation.
3 tbl, 5 ex