WO2019210764A1 - 冲动控制紊乱生物检测标记物和Impulsins的医药用途 - Google Patents
冲动控制紊乱生物检测标记物和Impulsins的医药用途 Download PDFInfo
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Definitions
- the present invention belongs to the field of biotechnology and relates to a marker, in particular to a method for detecting ATPase ATP13A2 gene mutation, sphingolipid abnormality causing nerve impulse control, behavioral and dyskinesia, and a class of therapeutic compounds called Impulsins, Impulsin -F1 (FTY720) or impulsin-F2 (Fluoxetine) have medical uses for impulsive control disorders associated with sphingolipid abnormalities, specifically involving FTY720 for preventing and controlling impulse control disorders (ICD) and motor ataxia, delirium and dementia Medical use, especially with FTY720 for impulsive control disorders and Parkinson's disease (PD), spastic paralysis, neuronal waxy lipofuscinosis and Kufor-Rakeb dementia in neurodegenerative diseases Medical use.
- ICD impulse control disorders
- Parkinson's disease PD
- spastic paralysis neuronal waxy lipofuscinosis and Kufor-Rakeb dementia in neurodegenerative diseases Medical use.
- Movement disorders caused by aging-related neurodegenerative diseases include Parkinson's disease (PD), Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuronal waxy lipofuscin Neuonal ceroid lipofuscinosis (NCL).
- PD Parkinson's disease
- SPG hereditary spastic paraplegia
- NCL neuronal waxy lipofuscin Neuonal ceroid lipofuscinosis
- Impulse control disorder itself is a clinically common behavioral abnormality, accounting for 3% of adults, usually early in the youth stage, but is significantly higher in patients with Parkinson's disease (25) -50%), especially in the process of dopamine replacement therapy, causes great pain to patients and relatives.
- Clinical diagnosis mainly depends on the evaluation of the consultation, and there is no effective and targeted treatment, which is a problem that needs to be solved for a long time.
- Impulsive control of behavior is an important mechanism of human and animal physiological behavioral norms, and is the result of the evolution of social life. For centuries, people have been concerned and wondering why abnormal behaviors of impulsive control have occurred in behavior. Although impulsive control abnormalities are common in young people, they also occur in adults and even lifelong, impulsive control disorder (ICD).
- TTM trichotillomania
- the pathological basis of impulsive control disorders may be related to the anterior vertebral dysfunction of the anterior frontal lobes (OFC).
- OFC anterior frontal lobes
- Neuroimaging in patients with Parkinson's disease also showed dysfunction of the OFC ventral region, including a weakened up-down control of the OFC, or excessive ventrolimbic activity in the brain, including the striatum marginal system, resulting in excessive impulse signals.
- OFC serotonin (5-HT) reduces the inhibition of the brain's impulses and rewards. This inhibition (called reversal learning) is a mechanism of behavioral flexibility that relies on the integrity function of the OFC-striatum loop.
- dopamine in the treatment of Parkinson's disease can induce impulsive control disorders.
- dopamine D3 receptor activity may be involved in mediating impulse control disorders, but some studies have pointed out that this is not the case. Studies have also shown that glutamate may participate in ICD, TTM, SP, and anxiety processes by linking the amygdala hypothalamus with cingulate gyrus and OFC in impulsive control disorders. Therefore, the balance of dopamine and glutamate activity in the regulation of cognitive flexibility of 5-HT receptor activity and regulation of intensive behavior, the striatum ventral nucleus and the anterior cingulate anterior region of OFC is impulsive regulation. Part of the physiological mechanism. Currently, Parkinson's disease-related genes associated with impulsive control disorders in patients with Parkinson's disease have not been identified.
- Lysosomes are membrane-like organelles of 0.1-1.2 micrometers. Through transmembrane translocation and fusion with other subcellular structures, lysosomes are taken up from the cells, or taken from the cells by cytoplasm, to the cytoplasm and the organelle environment. Steady state quality control is performed to regulate the homeostasis of the cellular microenvironment. Studies have shown that dysfunction of lysosomal membranes and decreased numbers are associated with degeneration of Parkinson's disease dopamine neurons. Lysosome damage causes lysosomal accumulation disorder (LSD), and some lysosomal accumulation disorder diseases such as Gaucher disease (GD) and Niemann-Pick disease (NPC) have the same molecular pathology as Parkinson's disease.
- LSD lysosomal accumulation disorder
- GD Gaucher disease
- NPC Niemann-Pick disease
- lysosomal SMPD1 and NPC1 gene mutations may be risk factors for Parkinson's disease. Therefore, lysosomal molecular function and metabolism may directly affect the structure and solubility of ⁇ -synuclein in neurons, and lysosomal dysfunction may promote the formation of eosinophilic inclusion bodies and neuronal aging and degeneration of Lewy bodies.
- the ATP13A2 (P-type ATPase) gene is a Parkinson's disease-causing gene located at the 1p36 locus of chromosome 1 at the 1p36 locus, encoding 1180 amino acids with 10 hydrophobic (transmembrane) regions.
- ATP13A2 plays an important role in regulating lysosomal homeostasis.
- a variety of ATP13A2 gene mutations have been found in young Parkinson's disease patients.
- ATP13A2 acts as a lysosomal transmembrane ATPase whose corresponding specific substrate ligand has not been determined.
- mice lacking ATP13A2 there is excessive ubiquitination of glial proteins, lipofuscinosis, endocytic pathway disorders, and age-related motor abnormalities similar to Parkinson's disease.
- ATP13A2 gene mutation Parkinson's disease is associated with a wider range of lysosomal damage, including lysosomal acidification, hydrolase processing and substrate degradation dysfunction, decreased autophagosome clearance, alpha-synuclein aggregation and cell death.
- the gene sequence and protein sequence of the ATP13A2 are shown in SEQ. No. 1-2 due to a decrease in serum sphingomyelin and an increase in ceramide due to ATPase ATP13A2 mutation.
- the invention provides an impulse control disorder biological detection marker, that is, a lysosomal membrane protein ATPase ATP13A2 mutation in a cell, a decrease in serum sphingomyelin and an increase in ceramide, and particularly relates to the behavior of Parkinson's disease accompanied by impulsive control disorder.
- Biodetection markers for abnormal movements Figure 1-6).
- a second object of the present invention is to provide a use of a class of compounds for the preparation of drugs for behavioral and motor abnormalities. Especially in the preparation of Parkinson's disease with impulsive control disorders, especially sputum spasm, standing and other abnormal movements, their behavior and dyskinesia drugs.
- the compounds are FTY720 and Fluoxetine.
- the present invention provides the use of FTY720 in the treatment of behavioral and motor abnormalities, in particular in the preparation of an effective drug for dyskinesia which is effective not only for impulsive control disorders of Parkinson's disease but also for neurodegenerative diseases such as spastic paralysis.
- Neurodegenerative diseases include Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuronal waxy lipofuscinosis (NCL).
- SPG hereditary spastic paraplegia
- NCL neuronal waxy lipofuscinosis
- FTY720 or Fingolimod the molecular formula is C 19 H 33 NO 2 .HCl, chemical name is 2-amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride, and the molecular weight is 343.94 g/mol.
- Impulsins impulsive inhibitors
- Impulsin-F1 a known ceramide-like compound FTY720.
- Another Impulsin-F2 known as Fluoxetine, has a compound that inhibits sphingomyelinase.
- FTY720 or Fingolimod C 19 H 33 NO 2 .HCl, chemical name 2-amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride, molecular weight 343.94g/mol
- FTY720 or Fingolimod C 19 H 33 NO 2 .HCl, chemical name 2-amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride, molecular weight 343.94g/mol
- FTY720 (Impulsin-F1) was intraperitoneally injected into the normal control group and the ATP13A2 knockout group, FTY720 (5 mg/kg/day), once a day for 1 week, FTY720 vs. normal mice.
- FTY720 ATP13A2-deficient mice.
- the post-drug ATP13A2 mice completely inhibited the animal's excessive mating behavior (Fig. 7A), excessive combing behavior (Fig. 7B), and completely restored the motor coordination function of the mice (Fig. 7C).
- FTY720 has the effect of treating impulsive control disorders and dyskinesias, with clear curative effect and complete therapeutic effect. It provides the only treatment for individuals with Parkinson's disease-like ataxia, spastic paralysis and impulsive disorder. And methods.
- the present invention provides the use of Fluoxetine for the preparation of a medicament for treating behavioral and motor abnormalities, in particular for the preparation of a medicament which is effective not only for the impulse control disorder of Parkinson's disease but also for dyskinesia of neurodegenerative diseases such as Parkinson's disease.
- the neurodegenerative diseases include Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuron waxy lipofuscinosis (NCL).
- SPG hereditary spastic paraplegia
- NCL neuron waxy lipofuscinosis
- Fluoxetine or fluoxetine also known as Prozac, has a chemical formula of C 17 H 18 F 3 NO.HCl and a molecular weight of 345.79. It is an approved clinical drug for antidepressants, obsessive-compulsive disorder, and fear.
- Fluoxetine (Impulsin-F2) was administered orally to normal control and ATP13A2 knockout mice, and Fluoxetine was low in ATP13A2 after 1 week of administration (20 mg/kg/d) in reference water. Rat behavior and motor abnormalities have significant inhibitory effects (Fig. 8A-D). The drug-treated ATP13A2 mice completely inhibited excessive combing behavior (Fig. 8A-B) and excessive mating behavior (Fig. 8C-D). Therefore, Fluoxetine has a clear effect on impulsive control disorders and is convenient for oral use.
- ATP13A2 deficiency caused excessive combing, plucking and skin self-harm.
- the ATP13A2 knockout mouse was inserted and the loxP locus was inserted on both sides of the 2-3 exon of the ATP13A2 gene.
- Genotyping and gene expression analysis confirmed the knockdown of ATP13A2 (Fig. 1A-D).
- ATP13A2-deficient mice had significant over-combination of hair, excessive tearing of the hair, and licking of the skin at 3-4 months of age (Fig. 2A-G). These mice developed bald spots or skin wounds on the back, neck, eyebrows, beard, cheeks, head or chest (Fig. 2A).
- ATP13A2 knockout mice spent more time on repetitive self-hair/hair pull at a certain position on their body surface than wild-type mice, and the number of episodes of grooming behavior was The average input time was three times that of the wild type control mice, and the female ATP13A2 knockout mice had higher incidence of hair tearing and licking skin than the male ATP13A2 knockout mice (Fig. 2B).
- the ATP13A2 knockout mouse hair was torn and licked, and the number and duration of seizures during the day and night increased significantly (Fig. 2B-D), accompanied by excessive anxiety and fear (Fig. 2E). Stress stimuli altered by circadian rhythms significantly aggravated excessive combing behavior (Fig. 2F).
- ATP13A2 knockout male mice sniffed the reproductive organs of another male mouse (Fig. 3J left) and mating (Fig. 3J right). Both were significantly higher than the control, and the behavior of ATP13A2 knockout males mating with homosexual mice increased 4-fold (Fig. 3J right). ATP13A2 knockout male mice also had a significantly higher genital taste preference for homosexual mice than wild-type mice (Fig. 3K). It can be seen that the apparent mating of ATP13A2 males is not only for females of different ages (Fig. 3I), but also for frequent mating with males of the same sex (Fig. 3J-K).
- ATP13A2 deficiency causes age-related dyskinesia.
- ATP13A2 deficiency caused excessive control of impulses, plucking, self-harming skin and excessive mating, and developed motor dysfunction after 12 months of age.
- 12-month-old ATP13A2 knockout mice developed from impulsive control to dyskinesia, including specific dysmotility in ATP13A2 knockout mice (Fig. 4A), showing small gait walking (Fig. 4B).
- Rotarod experiments showed that 3-6 months old ATP13A2-deficient mice already had motor coordination disorders (Fig. 4C).
- Neuron-specific knockdown of ATP13A2 also caused motor coordination disorders in mice of different ages (Fig. 4D).
- the hind limb tip angle (FBA) of ATP13A2 knockout mice was significantly reduced compared to wild type mice (Fig. 4E-F).
- the hindlimb standing behavior of ATP13A2 knockout mice was significantly reduced, which was 80% lower than that of wild control mice (Fig. 4G). This indicates that ATP13A2 deletion is similar to sputum sputum and ataxia gait defects in clinical Parkinson's disease, spastic sputum and NCL disorders.
- Sphingolipids include sphingomyelin (SM), ceramide (Ceramide, Cer), and sphingosine (Sphingosine, Sph).
- SM sphingomyelin
- Ceramide Ceramide
- Sphingosine Sph
- sphingomyelin accounted 80% of the sphingolipids, is a major cell membrane phospholipids on the formation and maintenance of membrane asymmetry between lipid rafts (Lipid rafts), cell communication and transport, play an important role 15.
- ATP13A2 was deficient, the sphingomyelin in the serum of the mice was significantly reduced compared with the wild type control group (Fig.
- ATP13A2 mutations characteristic changes in blood sphingolipids, especially sphingomyelin deficiency and increased ceramide, are associated with impulsive control behavior and dyskinesia.
- the invention provides a biomarker for detecting impulsive control disorder, namely ATP13A2 abnormality, blood sphingomyelin reduction and ceramide elevation; the invention also provides a ceramide analog compound FTY720 in impulse control disorder and/or dyskinesia preparation
- impulsive control disorder namely ATP13A2 abnormality, blood sphingomyelin reduction and ceramide elevation
- the invention also provides a ceramide analog compound FTY720 in impulse control disorder and/or dyskinesia preparation
- the invention provides a new therapeutic drug for clinical treatment of disorder of behavioral impulse control caused by sphingomyelin deficiency and ceramide increase.
- Figure 1 is a diagram showing the detection of allele and gene expression data of ATP13A2 knockout mice in one embodiment of the present invention.
- A Application of DNA probes to non-targeted gene regions revealed the gene size of normal ATP13A2 in control animals and the truncated ATP13A2 gene in knockout animals.
- B C: Detection of gene knockout results using probes against exogenous Neo DNA (B) and endogenous gene sequences.
- D Genotype analysis revealed that ATP13A2 knockout mice lack 2-3 exons.
- E ATP13A2 mRNA levels in mouse brain and liver tissues were detected by reverse transcription PCR.
- F RT-PCR and immunoblotting were used to detect ATP13A2 gene expression and protein levels in different regions of the brain.
- A Photograph of region-specific hair loss ATP13A2 lacks photographs of mice.
- B The incidence of plucking in mice aged 3-4 months. Mean, standard error, and p-value are observations for 50 animals per group.
- G Photographs of excessive skin loss and self-mutilation leading to severe skin damage.
- Figure 3 is a graph showing the detection of ATP13A2 deficiency in male erectile dysfunction and mating disorder data in one embodiment of the present invention.
- A ATP13A2 male rats of different ages chase the female frequency. The number of times the male rats chased the female rats within 25 minutes after the start of cohabitation was recorded by n. 24 by cohabiting the male rats in captivity with the prepared wild-type females.
- B: ATP13A2 lacks the frequency of male mice to smell the genitals of female mice, n 24.
- K: ATP13A2 lacks the reproductive odor preference of male and female mice. The genital secretions applied to the slides were scented by the mice, and the number of times the nose and mouth were exposed to the secretions on the slides within 3 minutes was recorded, n 10.
- Figure 4 is a graph showing the detection of ATP13A2 deficiency causing dyskinesia in one embodiment of the invention.
- A Imaging findings of limb contracture and relaxation disorders.
- B The gait abnormality and the length of the shortening step. The figure above shows the quantitative measurement of the step length. The figure below shows the representative mouse footprint.
- C Coordination ability damage. The mice were placed on a rotating rod and the rotating rods were rotated at different speeds (20 rpm for 3-6 months, 15 rpm for 12-18 months, 5 rpm for 24 months). The time the animal remained on the rotating rod was recorded three times per test. 15 animals per group.
- E 24-month-old ATP13A2 knockout mice showed foot valgus in the walking disorder, showing that the foot formed by the toe position is different from the foot-base angle (FBA) (wild animal blue line, ATP13A2 knockout red line) ).
- 5-6 are graphs showing changes in lipidomics in serum of ATP13A2-deficient mice in one embodiment of the present invention, the data showing that lack of ATP13A2 causes a decrease in sphingomyelin in mice and an increase in ceramide.
- Wild-type and ATP13A2 knockout mice each used 50 microliters of serum for methanol (500 ⁇ l) and chloroform extraction, and 1:1 butanol/methanol (BuOH/MeOH) suspension of lipids for liquid phase mass spectrometry. Combined (LC/MS) analysis.
- 5A sphingomyelin
- 5B ceramide
- 5C lysosomal phosphatidylcholine
- 5D phosphatidylcholine
- 6A fatty acid
- 6B lysosomal phosphatidylethanolamine
- 6C phosphatidylethanolamine
- 6D phosphatidyl Inositol.
- FIGS. 7-8 are graphs showing the effects of FTY720 (Impulsin-F1) on ATP13A2 deficiency-induced behavior and dyskinesia in mice in one embodiment of the present invention.
- FTY720 Impulsin-F1
- ATP13A2 deficiency-induced behavior and dyskinesia in mice in one embodiment of the present invention.
- 3-6 months old wild-type and ATP13A2 knockout mice received FTY720 (Impulsin-F1, 5 mg/kg/day, 50 ⁇ l) intraperitoneal injection for one week after receiving saline injection for one week and observing behavioral and motor phenotypes. Then, it was recorded and compared whether the effects of FTY720 (Impulsin-F1) on behavior and exercise had different effects compared to saline.
- 7A Effect of FTY720 (Impulsin-F1) on mating behavior of male ATP13A2-deficient mice.
- 7B Effect of FTY720 (Impulsin-F1) on the combing behavior of female ATP13A2 deficient mice.
- 7C Effect of FTY720 (Impulsin-F1) on the behavior of rod movement in ATP13A2-deficient mice.
- Asterisk(*) p ⁇ 0.05.
- 8A-D Fluoxetine (Impulsin-F2) has no obvious toxic side effects in normal mice, but has significant inhibitory effects on behavioral abnormalities in ATP13A2-deficient mice.
- Figure 9 is a graph showing the effect of FTY720 (Impulsin-F1) on the dyskinesia and sputum caused by ATP13A2 deficiency in mice in one embodiment of the present invention.
- FTY720 Impulsin-F1
- ATP13A2 deficiency 18-month-old wild-type and ATP13A2 knockout female mice received FTY720 (Impulsin-F1, 0.5 mg/kg/day, -8 ml) after receiving a drinking water containing FTY720 (Impulsin-F1) for one week and observing the exercise phenotype.
- FTY720 Impulsin-F1
- 9A Effect of FTY720 (Impulsin-F1) on ATP13A2-deficient mouse standing experiments.
- 9B Effect of FTY720 (Impulsin-F1) on motor coordination ability of ATP13A2-deficient mice in the runner.
- Example 1 ATP13A2 mutation and/or decreased sphingomyelin in serum, increased ceramide and lysosomal phosphatidylethanolamine, are biomarkers of anxiety and behavioral and motor abnormalities, especially impulsive control disorders such as plucking and uncovering skin. Markers' disease, Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuronal waxy lipofuscinosis (NCL) markers:
- W9.5ES cells were injected into C57BL/6 blastocysts to generate ES cell chimeras with W9.5 donor and C57BL/6 receptors, and chimeric C57BL/6 mice were produced by breeding to obtain genetically modified genital lines. Delivery, by mating with C57BL/6 mice to obtain wt/floxP heterozygotes, and then mating with ROSA-26 site Cre recombinase transgenic mice (C57BL/6-OzCRE) to achieve gene knockout heterozygotes (wt/KO/ Cre), Exon 2-3 and pkg-neo framework knockouts with animal tail tissue genotyping and gene expression assays (Figure 1). The animal's behavioral phenotype is obtained through real-time video observation, statistical analysis at different time periods, and statistical comparison analysis to obtain significant differences.
- ATP13A2 gene knockout had no significant effect on animal development, birth, growth and survival.
- the loss of ATP13A2 function causes impulsive control of the fur in mice, abnormal combing of excessive combing, plucking, and scratching of the skin, especially in young or younger females.
- Specific manifestations of these behaviors include repeated local combing of specific local areas, pulling and pulling out hair, resulting in loss of hair in different parts of the mouse, such as the face, eyes, forehead, head, neck and back, and Abdomen, etc.
- Fig. 2A Behavioral abnormalities occur more frequently in females than in males, with time to day or night (Fig. 2B-D) and anxiety and fear behavior (Fig. 2E).
- Example 2 ATP13A2 mutation and/or decreased sphingomyelin in serum, increased ceramide and lysosomal phosphatidylethanolamine, are markers of mammalian male impulse control abnormalities such as mating hypermutation and homosexual mating
- Experimental subjects wild type and ATP13A2 gene mutation C57BL/6 experimental mice.
- Example 3 ATP13A2 deficiency or dysfunction, and/or decreased sphingomyelin in serum, increased ceramide and lysosomal phosphatidylethanolamine, are biomarkers of mammalian aging and related neurodegenerative diseases, especially Parkinson's disease, Kufor-Rakeb dementia, hereditary spastic paraplegia (SPG), and neuronal waxy lipofuscinosis (NCL) caused by dysregulation, sputum markers:
- Experimental subjects wild type and ATP13A2 gene mutation C57BL/6 experimental mice.
- Example 4 A class of compounds, Impulsins, is an effective method for the treatment of impaired dyskinesia and dyskinesia such as Parkinson's disease:
- FTY720 (Impulsin-F1, 5 mg/kg, 50 ⁇ l) was intraperitoneally injected once a day before the test.
- the chemical structure of FTY720 is: 2-amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride, and the molecular weight is 343.94.
- One week after the injection changes in behavior and motor function of wild-type and ATP13A2-deficient animals were compared before and after injection. Animal behavioral phenotypes are obtained through real-time video observations, statistics at different time periods, and statistical comparisons to obtain significant differences.
- FTY720 Impulsin-F1
- ATP13A2 lacking animal over-mating behavior was fully corrected (Fig. 7A), and the animal's excessive combing behavior was also completely corrected (Fig. 7B), and the animal's motor coordination dysfunction was also fully restored (Fig. 7C).
- Example 5 A class of compounds, Impulsins, is an effective method for the treatment of impaired dyskinesia and dyskinesia such as Parkinson's disease:
- Example 6 A class of compounds, Impulsin-F1, is an effective method for the treatment of spastic paraplegia (SPG) dyskinesia:
- FTY720 (Impulsin-F1) (0.5 mg/kg/day) was orally administered daily before the test.
- the chemical structure of FTY720 is: 2-amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride, and the molecular weight is 343.94.
- FTY720 (Impulsin-F1) has no obvious toxic side effects in normal mice, but has a significant therapeutic effect on standing disorders in ATP13A2-deficient mice (Fig. 9). After one week of treatment with this drug, ATP13A2 lacked animal standing dysfunction and paralysis (Fig. 9A), and the runner experiment showed a significant loss of ability (Fig. 9B), but both standing and coordinated motor dysfunction were recovered after one week of medication (Fig. 9A-B). ).
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Claims (7)
- 一种ATP酶ATP13A2在制备行为和运动异常检测标记物中的应用,其特征在于,所述行为和运动异常是神经冲动控制紊乱和运动障碍所致,所述ATP13A2的氨基酸序列如SEQ.No.1所示。
- 根据权利要求1所述的应用,其特征在于,所述神经冲动控制紊乱和运动障碍因ATP酶ATP13A2突变引起血清中鞘磷脂降低和神经酰胺升高。
- 根据权利要求1或2所述的应用,其特征在于,所述的神经冲动控制紊乱和运转障碍包括运动共济失调、瘫痪、痴呆,以及帕金森氏病、痉挛性瘫痪、神经元蜡样质脂褐质沉积病和Kufor-Rakeb痴呆症。
- 一种化合物FTY720在制备治疗行为和运动异常疾病的药物中应用,所述FTY720化学分子式为C 19H 33NO 2.HCl,分子量为343.94,其特征在于,所述行为和运动异常是神经冲动控制紊乱和运动障碍性所致,所述化合物包括其任何修饰或类似化合物。
- 根据权利要求4所述的应用,其特征在于,所述的神经冲动控制紊乱和运转障碍包括运动共济失调、瘫痪、痴呆,以及帕金森氏病、痉挛性瘫痪、神经元蜡样质脂褐质沉积病和Kufor-Rakeb痴呆症。
- 一种化合物Fluoxetine在制备治疗行为和运动异常疾病的药物中应用,所述Fluoxetine化学分子式为C 17H 18F 3NO.HCl,分子量为345.79,其特征在于,所述行为和运动异常是神经冲动控制紊乱和运动障碍性所致,所述化合物包括其任何修饰或类似化合物。
- 根据权利要求6所述的应用,其特征在于,所述的神经冲动控制异常和运转障碍包括运动共济失调、瘫痪、痴呆,以及帕金森氏病、痉挛性瘫痪、神经元蜡样质脂褐质沉积病和Kufor-Rakeb痴呆症。
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