The use of atipamezole for the treatment of male sexual impotence
(57) Abstract:The invention relates to medicine. A method for treatment of male sexual impotence by introducing atipamezole in certain ways in certain doses. Technical result: a new method for the treatment of male impotence. 1 Il. The present invention relates to a new therapeutic treatment of male sexual impotence by introducing atipamezole, which is the INN-approved generic name for 4-/2-ethyl-2,3-dihydro-1H-inden-2-yl/-IH-imidazole or its pharmaceutically acceptable salt accession acid.Male impotence is a sexual dysfunction related to the difficulties of achieving and/or maintain sufficient penile erection. It may occur as a result of various causes from a purely psychogenic to fully physical disorders. For the treatment of impotence has been used in both surgical and pharmacological treatment. Surgical treatment (implantation penisnula prostatic device) has been successfully used mainly in the case of pure organic disease. Various agents have been proposed for use as medicaments for lecheniena drug therapy for impotence, therefore, so far not found any wide approval.A significant number of works were devoted to the identification of neurotransmitters that are included in the facilitation and inhibition of male sexual behavior (see, e.g., Bitran, Hull, 1987. Neuroscience and Behavioral reotens. Noradrenalina neurotransmission obviously plays an important role.However, according to Bitran & Hull, as dopaminergic transmission, and serotonergically transmission also regulate the sexual behavior of men. Thus, mechanisms other than antagonism against alpha-2-adrenergic receptors may play a major role in the regulation of sexual behavior in men.Patent DE N 3943519 describes the use for the treatment of erectile dysfunction peptides genetically related to calcitonin. It also States that genetically related to the calcitonin peptides at the above indications may be used in combination with the alpha blocker receptors. However, it does not mention that atipamezol or selective antagonist of alpha-2-recetaron may be one applied for the treatment of erectile dysfunction.Atipamezol is a selective and potent2-adrenoreceptor antagonist is amatol was described, for example, in European patent EP 183492 as useful for the termination of detomidine.We have now discovered that this compound is also very effective to increase men's sexual ability on the model of the apes. This discovery confirms that atipamezole can be effective also for the effective therapy of male impotence in people.Other2-adrenoretseptory antagonist, yohimbine, usually used to treat male impotence. Yohimbine increases noradrenergicheskoy neurotransmission and has been reported about the increase in sexual ability in males animals, although results from different studies are contradictory.MacDonald et al (Ann. Clin. Res. 20, 1988, 298-310) indicate that it is not clear whether therapeutic effect of yohimbine through antagonism against alpha-2 receptors. If fentolamina, which is not selective alpha-I-adrenergic antagonist, local introduction in the cavernous body of the penis causes long-lasting and strong erection, and at the same time more specific antagonist of alpha-2-adrenoreceptor - idazoxan - with this introduction has no effect. Therefore, the effects of yohimbine p is the research Institute of the alpha-2-adrenergic receptors.Reid et al (Zancet, August 22, 1987, 421-423) argue that the beneficial effect of yohimbine detected for the first time only after 2-3 weeks of treatment. Unusual, but the effect of atipamezole detected almost immediately after injection, as shown by the following experiments.Atipamezol clearly has advantages over yohimbinum for this application because of its distinctive selectivity. The ratio of the selectivity 2/1for atipamezole 200-300 times higher than for yohimbine.In the experiment studied three males and one female macaques with amputated tails. The age of the males was 13, 16 and about 24 years. Age females - 6 years.During the period of the study, the test pair was placed in one square (0.6 x 0.9 x 1.2 m) with two departments. Between sessions and during the first 10 min of each session moving wall separates the male and female in each cage. The moving wall is made of iron rods. Monkeys can see and touch each other through the sliding wall. After intramuscular dose of the investigational drug (saline control) begin monitoring sexual behavior of the male, as described below. After 10 min of drug administration removed the sliding of stee observation period (30 min after drug administration) moving the wall back to the place. Each time exploring a new pair, the first three sessions were conducted as above, but without the introduction of drugs that allows you to habituate the animals to each other. These first three sessions are not included in the results.See the time availability and the duration of the next behavior: a study of the perineum, lifting, ejaculation, communication, courtship, direct aggression towards the female, yawning, scratching, gnashing of teeth, shaking the cells and Masturbation. This report provides only the number of ejaculations in each session, because it gives the most accurate indicator of the willingness of male sexual behavior. For the same reason, ejaculation, obtained by Masturbation and intercourse, were combined in the results.The experiments were conducted only once a day for seven days. Atipamezol was given every second day and the saline control during other days. Preliminary results on one monkey showed that there are no differences in the effect of atipamezole, if he is given every third or second day.The dose of atipamezole range from 0.01 to 0.3 mg/kg dissolved in saline to a final volume of approximately 0.2 ml of Each dose was tested 5-15 times on each monkey. Usignolo month. The order of testing each dose varies between monkeys for a possible counterweight to the serial effect. The difference in the number of ejaculations obtained for a given dose of atipamezole and the corresponding days of saline control, was used as a measure of the impact of atipamezole on sexual behavior. Now possible variation of the primary sexual activity /corresponding ejaculation during salt days can be minimized. Cases of ejaculations /percentage salt of days with one or more ejaculation/ during salt days were used as the main indicator of sexual activity each male. When the statistical evaluation of the data was used one way analysis of variance /ANOVA and student's t test. P < 0.05 is considered as significant difference.In the case of the introduction of saline /=control/ sexual activity /percentage of sessions with ejaculations obtained in respect of and/or Masturbation/ three male monkeys were 7%, 12% and 26%. The oldest male had the lowest, and the young male is the highest sexual activity in the control /= saline conditions/. Sexual activity of males in saline conditions or atipamezole not depended on estratega cyclical the number of ejaculations, depending on the dose, all three male monkeys /for each individually; P < 0,05 ANOVA; drawing a-C/. The lowest effective dose of atipamezole ranges from 0.01 to 0.08 mg/kg depending on the individual; the younger male, the lower the lowest effective dose. The average increase ejaculations caused by atipamezole three males, also depends on the dose and is trustworthy (P < 0,05, ANOVA; drawing D/. There have been no other behavioral effects caused by atipamezole, except for the increase of alertness /alertness/.The drug is preferably administered orally, through the mucous, intravenous, intramuscular, or transdermal. The preferred interval daily dose of approximately 0.01 to 1 mg/kg, preferably 0.05 to 0.3 mg/kg for intravenous, intramuscular, transmucosal or TRANS-dermal and 0.03-10 mg/kg for oral administration. A method for the treatment of sexual impotence in men, including the introduction of antagonist alpha-2-adrenergic receptors, characterized in that antagonists alpha-2-adrenergic receptors is atipamezol or its pharmaceutically acceptable salt accession acid, and when administered orally to a person the amount specified connection is 0.3 - 10 mg/kg/day, intravenous, intramuscular, transmutes
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with treating patients with uterine cervix cancer with relapses in parametral fiber and in case of no possibility for radical operative interference and effect of previous radiation therapy. During the 1st d of therapy one should intravenously inject 30 mg platidiam incubated for 1 h at 37 C with 150 ml autoblood, during the next 3 d comes external irradiation per 2.6 G-r. During the 5th d of therapy one should introduce the following composition into presacral space: 60 ml 0.5%-novocaine solution, 1 ml hydrocortisone suspension, 2 ml 50%-analgin solution, 1 ml 0.01%-vitamin B12 solution, 1.6 g gentamycine, 800 mg cyclophosphan, 10 mg metothrexate. These curative impacts should be repeated at mentioned sequence four times. The method enables to decrease radiation loading and toxic manifestations of anti-tumor therapy at achieving increased percent of tumor regression.
EFFECT: higher efficiency of therapy.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):
wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.
EFFECT: valuable medicinal properties of compounds.
16 cl, 9 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new 1-(p-thienylbenzyl)-imidazoles of the formula (I): , wherein indicated residues represent the following values: R(1) means halogen atom, (C1-C4)-alkoxyl, (C1-C8)-alkoxyl wherein one carbon atom can be replaced with heteroatom oxygen atom (O); R(2) means CHO; R(3) means aryl; R(4) means hydrogen halogen atom; X means oxygen atom; Y means oxygen atom or -NH-; R(5) means (C1-C6)-alkyl; R(6) means (C1-C5)-alkyl in their any stereoisomeric forms and their mixtures taken in any ratios, and their physiologically acceptable salts. Compounds are strong agonists of angiotensin-(1-7) receptors and therefore they can be used as a drug for treatment and prophylaxis of arterial hypertension, heart hypertrophy, cardiac insufficiency, coronary diseases such as stenocardia, heart infarction, vascular restenosis after angioplasty, cardiomyopathy, endothelial dysfunction or endothelial injures, for example, as result of atherosclerosis processes, or in diabetes mellitus, and arterial and venous thrombosis also. Invention describes a pharmaceutical composition based on above said compounds and a method for their applying also.
EFFECT: valuable medicinal properties of compounds and composition.
10 cl, 19 ex
FIELD: organic chemistry and pharmaceutical compositions.
SUBSTANCE: invention relates to new 3-(5)-heteroaryl-substituted pyrazoles of formula I , tautomers or pharmaceutically acceptable salt of compounds and tautomers. In formula R1 is hydride, piperidinyl substituted with methyl, lower alkyl optionally substituted with halogen, hydroxyl, lower alkylanimo or morpholino; R2 is hydride, lower alkyl, amino, aminocarbonylamino, lower alkylaminocarbonylamino, lower alkylsulfonylamino, aminosulfonylamino, lower alkylaminosulfonylamino; Ar1 is phenyl optionally substituted with one or more independently selected halogen; HetAr2 is pyridinyl with the proviso that R2 is not amino or n-propyl when HetAr2 is pyridinyl; and HetAr2 is not 2-pyriridinyl when R2 is hydrogen or lower alkyl. Compounds of formula I have kinase p38 inhibitor activity and are useful in pharmaceutical compositions for treatment of various diseases.
EFFECT: new effective kinase p38 inhibitors.
23 cl, 6 dwg, 1 tbl, 1 ex
FIELD: veterinary science.
SUBSTANCE: a dog should be introduced with 4-[3-(difluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-il]benzene sulfonamide or its pharmaceutically acceptable salt at daily dosage ranged about 0.1-10 mg/kg body weight.
EFFECT: higher efficiency of therapy.
4 cl,262 ex, 12 tbl
FIELD: medicine, gynecology, anesthesiology.
SUBSTANCE: invention concerns to a method for carrying out the anesthesiology assistance for woman in childbirth with accompanying bronchial asthma. Method involves administration of atropine, dimedrol, analgin and clophelin. Method involves additional intravenous administration of transamine for 5-7 min. Transamine is administrated in doses 12-14 and 15-17 mg/kg in woman in childbirth with body mass 75 kg and above and 74 kg and less, respectively. Method provides enhancing quality and safety of anesthesia in this class of woman in childbirth.
EFFECT: improved assistance method.
7 tbl, 4 ex
FIELD: medicine, dermatology, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to an antifungal gel pharmaceutical composition based on ketoconazole and clotrimazole that are derivatives of imidazole. The composition comprises ketoconazole or clotrimazole as an active component, polyethylene glycol-400 (PEG-400) as a solvent, carboxyvinyl polymer as a gel-forming agent, polyethylene glycol as a gel stabilizing agent, organic amine or inorganic bas as a regulator of pH and water taken in the definite ratio of components. The composition is prepared by dissolving active component in PEG-400, dispersing carboxyvinyl polymer in water, successive addition to dispersion propylene glycol as a stabilizing agent and regulator of pH and combination of prepared solution and gel followed by stirring the mixture up to preparing the gel composition with pH 5-7. Invention provides preparing antifungal composition with reduced adverse effect.
EFFECT: improved preparing method, valuable medicinal properties of composition.
2 cl, 1 tbl, 11 ex
FIELD: veterinary science.
SUBSTANCE: the present innovation deals with applying selector as a selenium-containing organic preparation to be introduced for cows and calves monthly intramuscularly at the dosage of 10 mcg/kg body weight. The method provides decreased fodder expenses for the synthesis of the production obtained.
EFFECT: higher productivity in cattle.
2 ex, 7 tbl
FIELD: organic chemistry, medicine, allergology, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to a method for treatment of patient suffering with allergic disease. Method involves administration to patient the therapeutically effective dose of pharmaceutical composition comprising compound of the formula (I)
. The compound elicits high effectiveness in treatment of allergy and shows low toxicity also.
EFFECT: improved method for treatment.
9 cl, 2 tbl, 2 dwg, 40 ex
FIELD: veterinary science.
SUBSTANCE: one should apply a selenium-containing preparation named selecor: it should be introduced on the 80-90th d of swine gestation twice at 10-15-d-long interval parenterally at the dosage of 20 mg/kg animal body weight. Application of low-toxic antioxidant as selecor enables to improve functional properties of cell membranes of placental system and endometrium and increase inspecific immune resistance in sows. It, also, enables to increase fertility in sows, values of uncomplicated deliveries and puerperal period.
EFFECT: higher viability of off-spring.
2 ex, 3 tbl