58 results about "Serotonin 1A Receptor" patented technology

The present invention relates to a method of treating a patient suffering from a disorder of the central nervous system associated with 5-HT1A receptor subtype, comprising as an active ingredient a carbostyril derivative or a salt thereof represented by the formula (1): wherein the carbon-carbon bond between 3- and 4-positions in the carbostyril skeleton is a single or a double bond.

The present invention relates to a compound represented by the following formula, a pharmacologically acceptable salt thereof, or a use thereof as a pharmaceutical: wherein R1 and R2 are substituents adjacent to each other, and together with two carbon atoms to each of which they attach, form a 5- to 7-membered non-aromatic carbocyclic group or the like, which may be substituted by 1 to 4 substituents selected from (1) an oxo group, (2) a hydroxyl group, and the like; R3 represents a hydrogen atom or the like; and R6 represents a hydrogen atom or the like. It is an object of the present invention to discover an agent for treating or preventing lower urinary tract symptoms, and particularly symptoms regarding urinary storage, which has a superior strength of binding to a 5-HT1A receptor and an antagonism to the receptor.

The invention provides a new indole compound, pharmaceutically acceptable salts and medicinal preparations thereof, and a use of the new indole compound in selective inhibition of 5-hydroxytryptamine reuptake and / or excitation of a 5-HT1A receptor. The invention also relates to medicinal compositions comprising the compounds, and a method for treating the central nervous system dysfunction of mammals, especially humans by using the medicinal compositions.

The present invention provides a means for prevention and treatment of sarcopenia by administration of a substance that both reduces the sensibility of beta-adrenergic receptors and of 5-HT1a receptors. (S)-pindolol, (S)-propanol, tertalol, or bopindolol are preferred for this purpose.

The present invention relates to a compound represented by the following formula, a pharmacologically acceptable salt thereof, or a use thereof as a pharmaceutical: wherein R1 and R2 are substituents adjacent to each other, and together with two carbon atoms to each of which they attach, form a 5- to 7-membered non-aromatic carbocyclic group or the like, which may be substituted by 1 to 4 substituents selected from (1) an oxo group, (2) a hydroxyl group, and the like; R3 represents a hydrogen atom or the like; and R6 represents a hydrogen atom or the like. This compound has a superior strength of binding to a 5-HT1A receptor and an antagonism to the receptor, and is useful as an agent for treating or preventing lower urinary tract symptoms, and particularly symptoms regarding urinary storage.

A substituted 4-, 5-, 6-, and 7-indole derivative of Formula (I)wherein A is a group having formula (IIA), (IIB), (IIC)wherein X, U, Y, R3 to R12, Z, W, n and m are as defined above. The compounds are potent serotonin reuptake inhibitors and have 5-HT1A receptor antagonistic activity.

The present invention relates to a substituted piperazine compound and a use method and use thereof, and further relates to a pharmaceutical composition comprising the substituted piperazine compound and use thereof, wherein the substituted piperazine compound is a compound shown as formula (I) or a stereoisomer, tautomer, nitrogen oxide, solvate, metabolism product, a pharmaceutically acceptable salt or prodrug of the compound shown as the formula (I). The substituted piperazine compound and the pharmaceutical composition comprising the substituted piperazine compound can be used to inhibit 5-hydroxytryptamine reuptake and / or 5-HT1A receptor excitement. The invention also relates to a method for making the substituted piperazine compound and the pharmaceutical composition comprising the substituted piperazine compound, and relates to the use of the substituted piperazine compound and the pharmaceutical composition comprising the substituted piperazine compound in the treatment of central nervous system dysfunction.

The present invention relates to indole and 2,3-dihydroindole derivatives having formula (I)or any of its any of its enantiometers or any mixture thereof, or an acid addition salt thereof, wherein A, R1, R2, R3, W, X, Y and Z are as described in the description. The compounds are potent serotonin reuptake inhibitors and have 5-HT1A receptor antagonistic activity.

Disclosed herein are compositions and methods for treating depression using compositions comprising a compound of formula I. Disclosed herein are compositions and methods for treating depression using compositions comprising phenoxypropylamine compounds and derivatives having selective affinity for and antagonistic activity against the 5-HT1A receptor, as well as 5-HT reuptake inhibitory activity. In addition, compositions and methods for treating depression using compositions comprising a compound of formula II are disclosed. Methods of treating or diminishing at least one symptom of depression in a human subject with a composition comprising a compound of the formula (I) or formula (II), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, are also disclosed.

Contemplated substituted arylpiperazinyl compounds, and most preferably 18F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with 18F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain.

The present invention discloses a piperazine (piperidine) cyclohexyl derivative and applications of the piperazine (piperidine) cyclohexyl derivative in treatment of neuropsychiatric diseases. According to the present invention, the pharmacological experiment results show that the piperazine (piperidine) cyclohexyl derivative provides high affinity with a dopamine D2 receptor, a dopamine D3 receptor, a serotonin 5-HT1A receptor and a serotonin 5-HT2A receptor, provides good D3 / D2 receptor selectivity and good 5-HT1A / 5-HT2A receptor selectivity, and provides low affinity with alpha receptor; the in vivo test results show that the preferred compound has characteristics of good anti-schizophrenia effect, good pharmacokinetic property, low side effect, low acute toxicity and high safety, and has the development value of being adopted as the novel efficient and low-toxic anti-neuropsychiatric disease; and the piperazine (piperidine) cyclohexyl derivative is a compound represented by the structural general formula (I), or a geometric isomer, an optical isomer, a salt, a hydrate or a solvate thereof. The formula (I) is defined in the specification.

The invention relates to an aporphine compound represented by general formula (I) or stereoisomer thereof, pharmaceutically acceptable salt or pharmaceutically acceptable solvate and medical application thereof. The compound can be used for preventing or treating diseases related with serotonin 1A receptors, wherein the diseases comprise central nervous system diseases, in particular schizophrenia, depression and movement disorder caused by Parkinson's resistant medicament. The invention also relates to a medicinal composition comprising the compound.

The invention provides a pharmaceutical composition comprising a 5-HT1A receptor stimulant and a mood stabilizer. In the pharmaceutical composition, the weight ratio of the 5-HT1A receptor stimulant to the mood stabilizer is (1-40):(50-800). The invention also provides application of the pharmaceutical composition. Through combination of selective 5-HT1A receptor stimulant and the mood stabilizer which have different action mechanisms, the drug can treat anxiety, depression and / or biphasic emotional disorder and the like at the same time; the disease treatment spectrum is wider; furthermore, the curative effect after combination is more significant than that of single medicine, and the toxic and side effects are lower; a novel drug selection is provided to patients who are intolerant to first-line anti-anxiety or anti-depression or drugs.

The present invention relates to novel piperazine derivatives or pharmaceutically acceptable salts thereof, a process for preparing the same, and in particular, a high binding for Serotonin 1A(5-hydroxytryptamine; 5-HT1A) receptor, a pharmaceutical composition for treatment and / or prevention of depression and anxiety including an effective amount of the piperazine compound, and a method of treating depression, anxiety and other conditions related to 5-HT1A receptor in a mammal.

There is provided a selective serotonin reuptake inhibitor having affinity for serotonin 1A receptors which comprises a cyclic amine represented by the formula: wherein G represents a formula (2): a prodrug of said cyclic amine, or a pharmaceutically acceptable salt of said cyclic amine or prodrug, as an active ingredient.

The present invention relates to indole and 2,3-dihydroindole derivatives having formula (I)or any of its any of its enantiometers or any mixture thereof, or an acid addition salt thereof, wherein A, R<1>, R<2>, R<3>, W, X, Y and Z are as described in the description. The compounds are potent serotonin reuptake inhibitors and have 5-HT1A receptor antagonistic activity.

The invention discloses a sustained release preparation of tandospirone citrate with the 5-HT1A receptor stimulating effect, and a preparation method of the sustained release preparation. The preparation contains tandospirone citrate, a hydrophilic gel material and a wax material at a certain ratio, and an appropriate amount of filler and an appropriate amount of lubricant are added. The sustained release preparation has the effect of maintaining 24h sustained release, meanwhile, during the release period of medicines, no burst release risk exists, the medicine release uniformity is good, a preparation process is simple, the controllability of the process is strong, after medication, the too large blood concentration fluctuation is avoided, and the medication safety, effectiveness and compliance are improved.

The invention relates to a combined medicine for treating leukemia, and application of the combined medicine. The combined medicine is prepared from 5-HT1A receptor agonist and busulfan. The combinedmedicine has a remarkable treatment effect in treatment of the leukemia, especially treatment of chronic myelogenous leukemia; compared with the singly used busulfan, the combined medicine is better in treatment effect; the combined medicine has a synergistic effect.

The present invention provides a means for prevention and treatment of cachexia and other chronic illnesses including but not limited to the promotion of weight gain, reduction or prevention of weight loss by administration of a substance that both reduces the sensitivity of beta-adrenergic receptors and of 5-HT1a receptors. (S)-pindolol, (S)-propranolol, tertatolol or bopindolol are preferred for this purpose.

The invention relates to a non-catechol aporphine compound as well as a pharmaceutic composition and application thereof, in particular to a non-catechol aporphine compound shown as a general formula (I) or a stereoisomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate and medical application thereof. The compound can be used for preventing or treating diseases related with serotonin 1A receptors, comprising central nervous system diseases, particularly schizophrenia, depressions and dyskinesia caused by medicaments for resisting parkinson's diseases. The invention also relates to the medical composition containing the compound.

Disclosed is a FAST (Flexible Accelerated STOP TetO-knockin) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. This invention further discloses a single gene targeting event yielding 2 distinct knockin mice—STOP-tetO and tetO knockin—which permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue; 3) tTA-mediated misexpression; 4) tTA-mediated overexpression; and 5) tTS-mediated conditional knockout / knockdown. Using the FAST system, multiple gain- and loss-of-function strains can therefore be generated on a timescale not previously achievable. These strains can then be screened for clinically-relevant abnormalities. The flexibility and broad applicability of the FAST system is demonstrated by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, Neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

The invention belongs to the field of pharmacy, relates to medicinal use of an indole piperazine derivative, and in particular relates to appetency of the indole piperazine derivative to dopamine D3 receptor and 5-HT1A and 5-HT2A receptors, function characteristics and use in preparation of medicines for nervous system disease; adrenergic beta-2 receptor crystal structure is used as a template for the construction of a dopamine 5-HT1A receptor model; by accuracy verification on the receptor model and molecular dynamics simulation, a flexible receptor conformation can be obtained; active sites of the flexible receptor conformation can be detected; detection results are superimposed and a dynamic receptor effective-mass model is constructed; an existing compound database is screened and the activity is tested; and results show that the screened compound FDFWHF003 and its derivatives have good activity to the dopamine receptor and 5-HT receptors, can be used for preparation of anti-schizophrenia medicines, and especially is suitable for the preparation of medicines for treating schizophrenia caused by dopamine system and 5-HT system functional disorders.

The invention belongs to the field of pharmacy, relates to medicinal use of an indole piperazine derivative, and in particular relates to appetency of the indole piperazine derivative to dopamine D3 receptor and 5-HT1A and 5-HT2A receptors, function characteristics and use in preparation of medicines for nervous system disease; adrenergic beta-2 receptor crystal structure is used as a template for the construction of a dopamine 5-HT1A receptor model; by accuracy verification on the receptor model and molecular dynamics simulation, a flexible receptor conformation can be obtained; active sites of the flexible receptor conformation can be detected; detection results are superimposed and a dynamic receptor effective-mass model is constructed; an existing compound database is screened and the activity is tested; and results show that the screened compound FDFWHF003 and its derivatives have good activity to the dopamine receptor and 5-HT receptors, can be used for preparation of anti-schizophrenia medicines, and especially is suitable for the preparation of medicines for treating schizophrenia caused by dopamine system and 5-HT system functional disorders.

The invention discloses a compound having dual functions to 5-HT and application thereof in depressive disorder treatment. The formula is shown in the description, wherein R1, R2, R3 and R4 are independently selected from H, F or OH. In recent years, an antidepressant having the dual functions of 5-hydroxytryptamine 1A acceptor partial agitation and selective 5-hydroxytryptamine re-uptake inhibition becomes a hot point direction of a novel antidepressant drug research. In a [3H]5-HT uptake inhibiting effect experiment of a rat synaptosome and a h5-HT1A combined affinity experiment, the compound is verified to have the 5-HT re-uptake inhibiting effect and the agitating effect to a 5-HT1A acceptor. The fact that the compound can be used as a drug for treating human central nervous system disorders, such as a depressive disorder and an anxiety disorder, is demonstrated.

Contemplated substituted arylpiperazinyl compounds, and most preferably 18F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with 18F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain.

The present invention provides compositions and uses thereof for reducing anxiety and / or impulsivity, including, for example, suicidality, in a subject undergoing treatment with a serotonin reuptake inhibitor (SRI) comprising administering to the subject an effective amount of a SRI and an effective amount of a 5-HT1A receptor partial agonist / antagonist. In addition, the present invention provides dosing regimens for various SSRIs which can also reduce anxiety and / or impulsivity, including, for example, suicidality in a subject undergoing treatment with an SSRI. Kits including daily dosing regimens of various SSRIs are also provided.

The invention provides compounds of formula (I) wherein X represents O or S; n is 2, 3, 4, 5, 6, 7, 8, 9 or 10; m is 2 or 3; Y represents N, C or CH; and the dotted line represents an optional bond; R<1>, R<1'>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7>, R<8>, R<9>, R<10>, R<11> and R<12> are as defined in the description. The compounds are ligands of the 5-HT1a-receptor.

The present invention relates to sustained-release tablet formulations of piperazine-piperidine compounds, which can be useful in treating central nervous system disorders; to processes for their preparation; and to methods of using them.