Database : MEDLINE
Search on : Catalepsy [Words]
References found : 3400 [refine]
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[PMID]: 29378222
[Au] Autor:Lins LCRF; Souza MF; Bispo JMM; Gois AM; Melo TCS; Andrade RAS; Quintans-Junior LJ; Ribeiro AM; Silva RH; Santos JR; Marchioro M
[Ad] Address:Department of Physiology, Federal University of Sergipe, São Cristóvão, SE, Brazil.
[Ti] Title:Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine.
[So] Source:Brain Res Bull;139:9-15, 2018 Jan 30.
[Is] ISSN:1873-2747
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Parkinson's disease (PD) is a neurodegenerative disease characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc), with consequent depletion of dopamine in the striatum, which gives rise to the characteristic motor symptoms of PD. Although its etiology is unknown, several studies have suggested that oxidative stress plays a critical function in the pathophysiology of PD, and antioxidant agents could be helpful to slown down the dopaminergic neurodegeneration. Carvacrol (CA) is a phenolic monoterpene found in essential oils of many aromatic plants that presents antioxidant and neuroprotective effects. This study aimed to assess the effect of CA in a reserpine (RES)-induced rat model of PD. Male Wistar rats received 15 s.c. injections of 0.1 mg/kg RES or vehicle, every other day, concomitantly to daily i.p. injections of CA (12.5 or 25 mg/kg) or vehicle. Across the treatment, the animals were submitted to behavioral evaluation in the catalepsy test (performed daily), open field test (7th day) and assessment of vacuous chewing movements (12th, 20th and 30th days). Upon completion of behavioral tests, rats were perfused and their brains underwent tyrosine hydroxylase (TH) immunohistochemical analysis. Our results showed that CA (12.5 e 25 mg/kg) prevented the increase in catalepsy behavior and number of vacuous chewing movements, but failed to revert the decreased open-field locomotor activity induced by RES. In addition, CA in both doses prevented the decrease in TH immunostaining induced by RES in the SNpc and dorsal striatum. Taken together, our results suggest that CA shows a protective effect in a rat model of PD, preventing motor and neurochemical impairments induced by RES. Thus, the use of CA as a promising new strategy for the prevention and/or treatment of PD may be considered.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  2 / 3400 MEDLINE  
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[PMID]: 29247697
[Au] Autor:Vikhe S; Nirmal S
[Ad] Address:Department of Pharmacognosy, Pravara Rural College of Pharmacy, Loni 413736, Maharashtra, India. Electronic address: sunainavikhe@gmail.com.
[Ti] Title:Antiallergic and antihistaminic actions of Ceasalpinia bonducella seeds: Possible role in treatment of asthma.
[So] Source:J Ethnopharmacol;216:251-258, 2018 Apr 24.
[Is] ISSN:1872-7573
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:ETHNOPHARMACOLOGICAL RELEVANCE: Seed kernel of the plant Ceasalpinia bonducella Linn (Caesalpiniacaeae) are used for the treatment of asthma in folk medicine and ancient books. AIM OF STUDY: To assess the pharmacological efficacy of the plant in asthma and to confine and describe the synthetic constituents from the seeds that are in charge of the action. MATERIAL AND METHODS: The viability of petroleum ether, ethanol extract and ethyl acetate fraction from ethanol extract of C. bonducella seeds were screened for the treatment of asthma by various methods viz. effect of test drug on clonidine and haloperidol induced catalepsy, milk-induced leukocytosis and eosinophilia, mast cell stabilizing activity in mice and studies on smooth muscle preparation of guinea pig ileum (in-vitro). Column chromatography of active extract was done to pinpoint the active compound followed by structure elucidation by FTIR, GCMS and NMR spectroscopic methods. RESULTS: Ethyl acetate fraction from ethanol extract of C. bonducella seeds exhibited antihistaminic activity at the dose of 50 and 100 mg/kg, inhibited clonidine-induced catalepsy but not haloperidol-induced catalepsy. Ethyl acetate fraction from ethanol extract significantly inhibited increased leukocyte and eosinophil count due to milk allergen and showed maximum protection against mast cell degranulation by clonidine. The results of guinea pig ileum indicated that the compound 2 methyl, 1 hexadecanol isolated from ethyl acetate fraction of ethanol extract relaxed significantly the ileum muscle strips pre-contracted by which suggests the involvement of ß -agonists on the relaxation of the tissue. All the results are dose dependent. Active ethyl acetate fraction from ethanol extract showed presence of anti-asthmatic compound, 2-methyl, 1-hexadecanol. CONCLUSION: The ethyl acetate fraction from ethanol extract of seeds of the plant C. bonducella can inhibit parameters linked to asthma disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process

  3 / 3400 MEDLINE  
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[PMID]: 28454738
[Au] Autor:Miksys S; Wadji FB; Tolledo EC; Remington G; Nobrega JN; Tyndale RF
[Ad] Address:Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Canada. Electronic address: s.miksys@utoronto.ca.
[Ti] Title:Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.
[So] Source:Prog Neuropsychopharmacol Biol Psychiatry;78:140-148, 2017 Aug 01.
[Is] ISSN:1878-4216
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects.
[Mh] MeSH terms primary: Brain/drug effects
Brain/enzymology
Cytochrome P450 Family 2/metabolism
Haloperidol/adverse effects
[Mh] MeSH terms secundary: Animals
Brain/metabolism
Catalepsy/chemically induced
Haloperidol/blood
Liver/enzymology
Male
Microinjections
Nicotine/administration & dosage
Nicotine/pharmacology
Propranolol/administration & dosage
Propranolol/pharmacology
Rats
Tardive Dyskinesia/chemically induced
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:6M3C89ZY6R (Nicotine); 9Y8NXQ24VQ (Propranolol); EC 1.14.14.1 (Cytochrome P450 Family 2); J6292F8L3D (Haloperidol)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:170430
[St] Status:MEDLINE

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[PMID]: 29474898
[Au] Autor:Joseph E; Reddi S; Rinwa V; Balwani G; Saha R
[Ad] Address:Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, India. Electronic address: emil.joseph@pilani.bits-pilani.ac.in.
[Ti] Title:DoE based Olanzapine loaded poly-caprolactone nanoparticles decreases extrapyramidal effects in rodent model.
[So] Source:Int J Pharm;541(1-2):198-205, 2018 Feb 21.
[Is] ISSN:1873-3476
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The purpose of present investigation was to nano-encapsulate atypical antipsychotic such as Olanzapine in polymeric nanoparticles in order to explore the possibility of minimizing drug associated extrapyramidal adverse effects. The polymeric nanoparticulate systems were prepared using FDA approved polymer, polycaprolactone, by simple technique of nanoprecipitation using factorial design by DoE approach. The significant factors selected for the optimization during formulation development process were polymer content and surfactant concentration at three different levels (3 factorial design). The effect of selected significant factors were studied in depth on significant responses such as particle size and encapsulation efficiency. The optimized formulation was further surface modified with surfactant (polysorbate 80) so as to enhance the brain targeting efficiency of developed nanoparticles via endocytosis pathway. Furthermore, catalepsy was induced in rodent model and the designed formulations were investigated in comparison with pure drug solution for efficiency in decreasing extrapyramidal adverse effects. The results of in vitro characterization studies demonstrated a narrow size distributed nanoparticles (73.28 ±â€¯2.14 nm) with high stability indicating zetapotential (-32.46 ±â€¯1.15 mV) and high encapsulation efficiency (78.77 ±â€¯2.83%). In vitro release studies resulted in an extended release of atypical antipsychotic for 60 h from drug-loaded optimized nanoparticulate formulations. The catalepsy studies in rodent model demonstrated a significant decrease in extra pyramidal adverse effects as compared to the pure atypical antipsychotic. Thus, the designed antipsychotic loaded polymeric nanoparticulate system may be highly promising for the tremendous improvement of antipsychotic therapy with reduced adverse effects.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

  5 / 3400 MEDLINE  
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[PMID]: 29516413
[Au] Autor:Arora D; Mudgal J; Nampoothiri M; Mallik SB; Kinra M; Hall S; Anoopkumar-Dukie S; Grant GD; Rao CM
[Ad] Address:School of Pharmacy and Pharmacology, Griffith University, Gold Coast, QLD, 4222, Australia. d.arora@griffith.edu.au.
[Ti] Title:Interplay between adenosine receptor antagonist and cyclooxygenase inhibitor in haloperidol-induced extrapyramidal effects in mice.
[So] Source:Metab Brain Dis;, 2018 Mar 07.
[Is] ISSN:1573-7365
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Antipsychotic drugs are the mainstay of psychotic disorders. The 'typical' antipsychotic agents are commonly employed for the positive symptoms of schizophrenia, though at an expense of extrapyramidal side effects (EPS). In the present study, we employed haloperidol (HP)-induced catalepsy model in mice to evaluate the role of adenosine receptor antagonist and cyclooxygenase (COX) enzyme inhibitor in the amelioration of EPS. HP produced a full blown catalepsy, akinesia and a significant impairment in locomotion and antioxidant status. Pre-treatment with COX inhibitor; naproxen (NPx) and adenosine receptor antagonist; caffeine (CAF), showed a significant impact on HP-induced cataleptic symptoms. Adenosine exerts pivotal control on dopaminergic receptors and is also involved in receptor internalization and recycling. On the other hand, prostaglandins (PGs) are implicated as neuro-inflammatory molecules released due to microglial activation in both Parkinson's disease (PD) and antipsychotics-induced EPS. The involvement of these neuroeffector molecules has led to the possibility of use of CAF and COX inhibitors as therapeutic approaches to reduce the EPS burden of antipsychotic drugs. Both these pathways seem to be interlinked to each other, where adenosine modulates the formation of PGs through transcriptional modulation of COXs. We observed an additive effect with combined treatment of NPx and CAF against HP-induced movement disorder. These effects lead us to propose that neuromodulatory pathways of dopaminergic circuitry need to be explored for further understanding and utilizing the full therapeutic potential of antipsychotic agents.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1007/s11011-018-0201-y

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[PMID]: 29366825
[Au] Autor:Melo-Thomas L; Gil-Martínez AL; Cuenca L; Estrada C; Gonzalez-Cuello A; Schwarting RK; Herrero MT
[Ad] Address:Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, 35032, Marburg, Germany; Instituto de Neurociências & Comportamento - INEC, Campus USP, Ribeirão Preto, SP, 14040-901, Brazil; Marburg Center for Mind, Brain, and Behavior (MCMBB),
[Ti] Title:Electrical stimulation or MK-801 in the inferior colliculus improve motor deficits in MPTP-treated mice.
[So] Source:Neurotoxicology;65:38-43, 2018 Jan 31.
[Is] ISSN:1872-9711
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p < 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

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[PMID]: 29174294
[Au] Autor:Liu H; Jia L; Chen X; Shi L; Xie J
[Ad] Address:Collaborative Innovation Center for Brain Science, Department of Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Medical College of Qingdao University, 266071, China.
[Ti] Title:The Kv7/KCNQ channel blocker XE991 protects nigral dopaminergic neurons in the 6-hydroxydopamine rat model of Parkinson's disease.
[So] Source:Brain Res Bull;137:132-139, 2018 Mar.
[Is] ISSN:1873-2747
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The excitability of dopaminergic neurons in the substantia nigra pars compacta (SNc) that supply the striatum with dopamine (DA) determines the function of the nigrostriatal system for motor coordination. We previously showed that 4-pyridinylmethyl-9(10H)-anthracenone (XE991), a specific blocker of Kv7/KCNQ channels, enhanced the excitability of nigral DA neurons and resulted in attenuation of haloperidol-induced catalepsy in a Parkinson's disease (PD) rat model. However, whether XE991 exhibits neuroprotective effects towards DA neuron degeneration remains unknown. The aim of this study was to investigate the effects of Kv7/KCNQ channel blocker, XE991, on 6-hydroxydopamine (6-OHDA)-induced nigral DA neuron degeneration and motor dysfunction. Using immunofluorescence staining and western blotting, we showed that intracerebroventricular administration of XE991 prevented the 6-OHDA-induced decrease in tyrosine hydroxylase (TH)-positive neurons and TH protein expression in the SNc. High-performance liquid chromatography with electrochemical detection (HPLC-ECD) also revealed that XE991 partly restored the levels of DA and its metabolites in the striatum. Moreover, XE991 decreased apomorphine (APO)-induced contralateral rotations, enhanced balance and coordination, and attenuated muscle rigidity in 6-OHDA-treated rats. Importantly, all neuroprotective effects by XE991 were abolished by co-application of Kv7/KCNQ channel opener retigabine and XE991. Thus, Kv7/KCNQ channel inhibition by XE991 can exert neuroprotective effects against 6-OHDA-induced degeneration of the nigrostriatal DA system and motor dysfunction.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:In-Data-Review

  8 / 3400 MEDLINE  
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[PMID]: 29407591
[Au] Autor:Zajdel P; Kos T; Marciniec K; Satala G; Canale V; Kaminski K; Holuj M; Lenda T; Koralewski R; Bednarski M; Nowinski L; Wójcikowski J; Daniel WA; Nikiforuk A; Nalepa I; Chmielarz P; Kusmierczyk J; Bojarski AJ; Popik P
[Ad] Address:Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. Electronic address: pawel.zajdel@uj.edu.pl.
[Ti] Title:Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.
[So] Source:Eur J Med Chem;145:790-804, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacology profile of 62, characterized by partial 5-HT R agonism, 5-HT /5-HT /D /D R antagonism, and blockade of SERT, reduced the "positive"-like, and "negative"-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clinical efficacy should be verified in further stages of development.
[Mh] MeSH terms primary: Amines/pharmacology
Antipsychotic Agents/pharmacology
Cognition/drug effects
Receptors, Dopamine D2/metabolism
Sulfonamides/pharmacology
[Mh] MeSH terms secundary: Amines/chemical synthesis
Amines/chemistry
Animals
Antipsychotic Agents/chemical synthesis
Antipsychotic Agents/chemistry
Dose-Response Relationship, Drug
Guinea Pigs
HEK293 Cells
Humans
Male
Molecular Structure
Rats
Rats, Wistar
Structure-Activity Relationship
Sulfonamides/chemical synthesis
Sulfonamides/chemistry
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Amines); 0 (Antipsychotic Agents); 0 (Receptors, Dopamine D2); 0 (Sulfonamides)
[Em] Entry month:1803
[Cu] Class update date: 180302
[Lr] Last revision date:180302
[Js] Journal subset:IM
[Da] Date of entry for processing:180207
[St] Status:MEDLINE

  9 / 3400 MEDLINE  
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[PMID]: 29410018
[Au] Autor:Kabel AM; Omar MS; Alhadhrami A; Alharthi SS; Alrobaian MM
[Ad] Address:Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: ahmed.kabal@med.tanta.edu.eg.
[Ti] Title:Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-ß1, NF-κB and glucagon-like peptide 1.
[So] Source:Physiol Behav;188:108-118, 2018 Feb 08.
[Is] ISSN:1873-507X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. METHODS: Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-ß1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondrial complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination. RESULTS: The combination of l-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant improvement of the behavioural changes, striatal dopamine, antioxidant parameters, Nrf2/HO-1 content, GLP-1, ATP and mitochondrial complex I activity with significant decrease in striatal RAGE, TGF-ß1, TNF-α, IL-10, TLR4 and alleviated the immunohistochemical changes better than the groups that received either l-dopa/Carbidopa or linagliptin alone. CONCLUSION: The combination of l-dopa/Carbidopa and linagliptin might represent a promising therapeutic modality for management of parkinsonism.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[St] Status:Publisher

  10 / 3400 MEDLINE  
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[PMID]: 29324345
[Au] Autor:Xu M; Wang Y; Yang F; Wu C; Wang Z; Ye B; Jiang X; Zhao Q; Li J; Liu Y; Zhang J; Tian G; He Y; Shen J; Jiang H
[Ad] Address:CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
[Ti] Title:Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect.
[So] Source:Eur J Med Chem;145:74-85, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:In the present study, a series of multi-target N-substituted cyclic imide derivatives which possessed potent dopamine D , serotonin 5-HT and 5-HT receptors properties were synthesized and evaluated as potential antipsychotics. Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride (3d) held a promising pharmacological profile. 3d not only showed potent and balanced in vitro activities on D /5-HT /5-HT receptors, but also endowed with low to moderate activities on 5-HT , H , α , M receptors and hERG channel, suggesting a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In animal behavioral studies, 3d reduced phencyclidine-induced hyperlocomotion with a high threshold for catalepsy induction. Compound 3d was selected as a potential antipsychotic candidate for further development.
[Mh] MeSH terms primary: Antipsychotic Agents/pharmacology
Catalepsy/drug therapy
Imides/pharmacology
[Mh] MeSH terms secundary: Animals
Antipsychotic Agents/chemical synthesis
Antipsychotic Agents/chemistry
Catalepsy/chemically induced
Dose-Response Relationship, Drug
Humans
Imides/chemical synthesis
Imides/chemistry
Locomotion/drug effects
Male
Mice
Mice, Inbred ICR
Molecular Structure
Phencyclidine
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antipsychotic Agents); 0 (Imides); J1DOI7UV76 (Phencyclidine)
[Em] Entry month:1802
[Cu] Class update date: 180227
[Lr] Last revision date:180227
[Js] Journal subset:IM
[Da] Date of entry for processing:180112
[St] Status:MEDLINE


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