Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
  • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/24—Antidepressants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/26—Psychostimulants, e.g. nicotine, cocaine

Definitions

• the present invention relates to a new medicinal use of a 2- (1-piperazinyl) -cycloheptomidazole derivative known as an antihypertensive agent, and particularly useful for the treatment of mental illness in mammals including humans and a psychotropic drug. About the method. Background art
• the present inventors have studied various compounds which exhibit psychotropic effects, particularly antidepressant activity, have low toxicity, and can be used in combination with other psychotropic drugs. -(1-H. Perazinyl)-Detected that certain compounds contained in cycloheptimidazole derivatives have psychotropic effects, and cultivated the use of the known compounds as new therapeutic agents. Things.
• the present invention provides the following formula (I)
• the 2- (1-'d.perazinyl) -cycloheptoimidazole derivative described in the above-mentioned JP-A-56-125584 is extremely dependent on the type of the substituent R.
• Ri in the formula (I) of the present invention corresponding to the substituent R represents a hydrogen atom, formyl, methoxycanoleboninole, ethoxycanolebonyl, propoxy.
• the compound is a canoleboninole or an impoxycarbonyl group, the compound or a pharmacologically acceptable salt thereof has been found to have a psychotropic effect.
• the melting point (p) is based on the MP-85 trace melting point analyzer manufactured by Yanagi Head Office. Physical properties other than those described above are substantially the same as those described in Japanese Patent Publication No. 56-125384.
• Examples of pharmacologically acceptable salts of the compound of the formula (I) include, for example, inorganic salts such as hydrochloride, hydrobromide, sulfate, phosphate, acid phosphate, and acetic acid. Salt, benzoate, maleate, fumarate, succinate, tartrate, lactate, citrate, dalconate, malate, saccharate, methanesulfonate, V-toluenesulfone Organic acid salts such as acid salts can be exemplified.
• the compound represented by formula (I), which is an active ingredient of the psychotropic drug of the present invention, has a psychotropic effect, that is, an antipsychotic effect, particularly an antidepressant activity, and further has an anorectic activity in mammals including humans. And at least part of this activity is Norr ⁇ dani. It may result from the ability to enhance activity at either or both synapses of nephrin and / or serotonin.
• each compound of the present invention was measured in mice as shown in the following experimental examples. And tested antagonistically against apomorphine, reserpine, and tetrapenazine. In addition, the presence or absence of central anticholinergic effect, which is a major undesirable side effect of antidepressants, was examined using the drug's effect on tremor-induced tremor as an index. On the other hand, almost all of the compounds of the present invention have been found to have no effect, and are considered to be useful drugs for central nervous system in this regard.
• the term “drug” indicates a drug obtained by dissolving each compound of the present invention or the specific example in physiological saline or 0.5% carboxine methylcellulose saline (hereinafter abbreviated as CM), and is referred to as a solvent. In this case, it means physiological saline or CMC used as a control.
• CM physiological saline or 0.5% carboxine methylcellulose saline
• hypothermia induced by high doses of morphine is specifically antagonized by a number of antidepressants. J. Peuch et al.-
• mice Five-week-old ddF male mice were used in groups of 5 or 10 mice. 30 minutes after intraperitoneal administration of the drug or solvent or 0 minutes after administration of the drug. Morphine 1 ⁇ / was subcutaneously administered. 3 Q minutes after administration of amorphin, thermistor j. (Rectal temperature) was measured, and the inhibition rates,, and were calculated as compared with those of the control group, and the results were used as the efficacy. The results are shown in Table 1.
• mice used Experimental Example 2 Low usage amount. Resistance to morphine-induced hypothermia According to the method of Experimental Example 1, The dose of morphine is 1 /
• the compounds according to the present invention, B, C, and ⁇ inhibit the amorphin-induced hypothermia in a dose-dependent manner as in the control imipramine.
• the compounds of Comparative Examples, ⁇ and G did not suppress the decrease in body temperature.
• the high dose in Table 1 shows antidepressant activity and the low dose in Table 2 In some cases, it shows antimitotic activity and is active in both oral and parenteral administration.
• mice Thermistor;
• Mouse body temperature was measured before drug administration, immediately before reserpine administration, and 1, 2, 3, 4, 5, and 5 hours later, and the effect of drug on mouse normal body temperature and drug reserpine-induced The effects on body temperature in mice were investigated. The results are shown in Table 3.
• Tetrabenazine 32 was intraperitoneally administered to 10 mice orally, 10 minutes after oral administration of the drug or solvent. 50 minutes and 0 minutes after tetrapenazine administration, according to the following score: 1) Degree of eye drop (0: fully open, 1: + closed eyes, 2: + closed eyes, 3: + closed eyes, 4: closed eyes) The measured values were compared with those of the test drug-untreated group, and the inhibition rates,, and were calculated as the drug efficacy. The results are shown in Table 4.
• NE Function As shown in Table 5, the control imipramine suppressed tremor in a dose-dependent manner, whereas the compounds of the present invention, B and C
• mice Five weeks old dd Y male mice were used in each group.
• the drug was used in the form of a water-soluble drug suspended in physiological saline, and the others were suspended in 0.5 CC / physiological saline solution.
• the dose of drug was 0.1 for mice.
• Drugs were administered orally by gavage using an oral probe. Then, the progress of the mouse 24 hours after the drug administration was observed. Table 6 shows the results.
• the compounds of the present invention other structures similar 2 - (1 - arsenate 0 Perajiniru) - specific in their psychotropic effects in comparison with consequent opening hept I Mi Dazo Ichiru derivatives (See Tables 1 and 2). It differs from imipramine, the main antidepressant, in part of its action (see Table 5), and is effective as a psychotropic drug. These compounds can be used not only alone, but also in combination with imipramine in a time-shifted manner, or in combination with imipramine in a timely manner.] It can also be used in combination with other antidepressants, such as danpramine and amide. Triptylin, nortriptyline, amoxahi. Doksehi. Can also be used in combination with arginine, macrotilin, mianserin, fleafensin, pyroxazine, L-5-oxa and the like.
• the compounds of the present invention are used as psychotropic drugs in the form of various pharmaceutical compositions. Examples include tablets, granules, powders, capsules, syrups, Injection, suppository and the like can be mentioned. These preparations may be used as pharmaceutically acceptable diluents or carriers such as ordinary additives such as binders, excipients, disintegrants, lubricants, flavoring agents, preservatives, stabilizers and the like. Can be formulated by a conventional method. At this time, the content of the compound of the formula (I) or a pharmaceutically acceptable salt thereof may be, for example, about 0.2 to about 50% by weight based on the weight of the composition.
• the dosage of the psychotropic drug of the present invention varies depending on the age, health condition, weight, nature and degree of symptoms, presence / absence and type of other drugs for co-treatment, and the like.
• Examples of each dose are the powers that can be mentioned, but not limited to .
• a psychotropic drug effective amount of the compound of the formula (I) or a pharmaceutically acceptable salt thereof and a psychotropic drug comprising a pharmaceutically acceptable diluent or carrier can be provided.
• a psychiatric patient is administered with a psychotropically effective amount of the compound of the above formula (I) or a pharmacologically acceptable salt thereof.
• the present invention also provides a method for treating the compound of the formula (I) or a pharmaceutically acceptable salt thereof. Provides the use of salt as a psychotropic drug.
• Example 1 Capsule (hard) A capsule was prepared by filling a hard gelatin capsule with the following mixture using an ordinary capsule manufacturing apparatus.
• a cell was manufactured. C to give the product
• the capsules were dried after washing with petroleum ether
• Example 4 in which a tablet was manufactured
• composition Ampoule Active Ingredient 1 Sodium Canoleboxy Methynoresenorelose 0.76 Weight
• an oral preparation was prepared by a conventional method so that the above composition was contained.
• the 2- (1-hi.perazyl) -cycloheptymidazole derivative of the present invention is imif. Like Lamin, it can be effectively used as a psychotropic drug.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Medicinal Chemistry (AREA)
• Psychiatry (AREA)
• Neurology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Biomedical Technology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Neurosurgery (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pain & Pain Management (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=14689258

Family Applications (1)

Country Status (2)

Citations (1)

• 1984
  • 1984-06-08 JP JP59116524A patent/JPS60260516A/ja active Granted
• 1985
  • 1985-06-08 WO PCT/JP1985/000325 patent/WO1986000017A1/ja not_active Ceased

Patent Citations (1)

Also Published As

Similar Documents

Legal Events