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Pramipexole, a dopamine D3/D2 receptor-preferring agonist, attenuates reserpine-induced fibromyalgia-like model in mice

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Neural Regeneration Research 2022年第2期17卷 450-458页

作者： Carlos Pereira Martins Rodrigo Sebben Paes Gabriela Mantovani Baldasso Eduarda Gomes Ferrarini Rahisa Scussel Rubya Pereira Zaccaron Ricardo Andrez Machado-de-Avila Paulo Cesar Lock Silveira Rafael Cypriano Dutra Laboratory of Autoimmunity and Immunopharmacology Department of Health SciencesCampus AraranguaUniversidade Federal de Santa CatarinaAraranguáSCBrazil Post-Graduate Program of Neuroscience Center of Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisSCBrazil Laboratory of Experimental Physiopathology Program of Postgraduate in Science of HealthUniversidade do Extremo Sul CatarinenseCriciumaSCBrazil

Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.

关键词： dopamine dopaminergic system fibromyalgia hyperalgesia pain pramipexole reserpine

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No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study

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Journal of Geriatric Cardiology 2019年第8期16卷 608-613页

作者： Guo-Hua ZHU Xi-Peng SUN Jing LI Lin PI Hai-Qin TANG Hai-Qing GAO Hong-Liang CONG Peng QU Xin-Zheng LU Xin-Jun ZHANG Luo-Sha ZHAO Yi-Fang GUO Dong-Xia LIU Liang-Qing ZHANG Hua TANG Yi-Xin HU Li FAN Qi HUA Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Department of Geriatrics Hebei General HospitalShijiazhuangChina Department of Cardiology Hebei General HospitalShijiazhuangChina Department of Cardiology Shanxi Cardiovascular HospitalXianChina Department of Geriatrics Chinese PLA General HospitalBeijingChina Department of Cardiology Chuiyangliu Hospital affiliated to Tsinghua UniversityBeijingChina Department of Cardiology the First Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of Cadre Health Care Qilu Hospital of Shandong UniversityJinanChina Department of Cardiology Tianjin Chest HospitalTianjinChina Department of Cardiology the Second Hospital of Dalian Medical UniversityDalianChina Department of Cardiology Jiangsu Provincial HospitalNanjingChina Department of Geriatrics West China HospitalSichuan UniversityChengduChina Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Background reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient. Methods In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of “compound reserpine and triamterene tablets (CRTTs)” for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected. Results From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users (P = 0.7). The majority of study subject had a depression score reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users. Conclusions There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered;and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

关键词： Depression Hypertension reserpine

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reserpine-Induced Progressive Parkinsonism in Mice Predisposed and Non-Predisposed to Depressive-Like Behavior

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Journal of Behavioral and Brain Science 2021年第11期11卷 267-279页

作者： Manuela B. L. Soares Leonardo B. Lopes-Silva Marcela Becegato Vinicius S. Bioni Alvaro C. Lima Gabriela M. Ferreira Ywlliane Meurer Regina H. Silva Behavioral Neuroscience Laboratory Department of Pharmacology Federal University of S&atilde o Paulo S&atilde o Paulo Brazil Memory and Cognition Studies Laboratory Post-Graduate Program of Cognitive Neuroscience and Behavior Department of Psychology Federal University of Paraíba Jo&atilde o Pessoa Brazil

Parkinson’s disease (PD) is a progressive degenerative condition that mainly affects the elderly. The disease comprises motor symptoms such as tremors at rest, loss of voluntary movement, decreased muscle strength, propensity to lean forward and acceleration of the walking pace. These signs are related to the degeneration of the nigrostriatal dopaminergic pathway. Patients also have non-motor symptoms, among which sleep alterations, cognitive deficits, fatigue, pain and depression stand out. Although depression has been described as the most prevalent non-motor symptom, it is not clear whether this mood disorder is due to PD or patients would already have a greater predisposition. The present study evaluated the relationship between the predisposition to depressive-like behavior and the development of motor alterations in a progressive pharmacological model of PD in mice. Mice were classified into groups of depressive-like propensities and submitted to the pharmacological model. reserpine was administrated at 0.1 mg/kg on alternate days for 40 days. The catalepsy and oral movement tests were used to evaluate motor alterations, the sucrose preference test was used to evaluate anhedonia, and the open field test was applied to evaluate general activity. reserpine promoted parkinsonian motor impairments, and there were no differences between animals from different depressive-like behavior profiles. Thus, it was not possible to find a relationship between parkinsonism and the propensity to depression based on the basal sucrose preference test. More studies with other evaluations of depressive-like behavior are needed to confirm the results found in our study.

关键词： Parkinson’s Disease Depression reserpine Mice

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reserpine Improves Working Memory

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Journal of Behavioral and Brain Science 2016年第3期6卷 107-112页

作者： Raghuraman Vasantharaja Ajeet Kumar Ashok Kumar Jamuna R. Subramaniam Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur India Center for Preclinical and Translational Medicine Research Central Research Facility Sri Ramachandra University Chennai India

Despite exhaustive search, no drug is in sight for AD. Earlier, we reported that reserpine, an antihypertensive and antipsychotic drug, ameliorates Amyloid beta (Aβ-AD causing peptide) toxicity and confers several positive enhancements in the C. elegans model system. Here, we evaluate whether reserpine can provide protection against working memory and against AD in the mouse model. reserpine (0.08 mg) was administered orally on alternate days to the non-Tg and accelerated Aβ deposition (at 2 months of age)and cognitive deficit (4 months of age) developing 5XFAD AD Tg mouse model expressing mutant human APP (3 familial mutations) and human Presenilin1(2 familial mutations) in the neurons, and follow their working memory for 2 months using the spontaneous Y-maze alteration behavioral paradigm. reserpine enhanced working memory in non-Tg mice and improved the cognitive deficit in the 5XFAD AD Tg mice. Hence, reserpine can be considered for a detailed evaluation in the 3X Tg AD mouse model and a pilot study in AD patients.

关键词： Alzheimer’s Disease Amyloid-β-Aβ reserpine Cognitive Deficits Transgenic Mice Working Memory

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Crystal structures of MdfA complexed with acetylcholine and inhibitor reserpine

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Biophysics Reports 2016年第Z1期2卷 78-85页

作者： Ming Liu Jie Heng Yuan Gao Xianping Wang College of Biotechnology Tianjin University of Science and Technology National Laboratory of Macromolecules National Center of Protein Science-Beijing Institute of BiophysicsChinese Academy of Sciences

The DHA12 family of transporters contains a number of prokaryotic and eukaryote membrane proteins.Some of these proteins share conserved sites intrinsic to substrate recognition, structural stabilization and conformational changes. For this study, we chose the Mdf A transporter as a model DHA12 protein to study some general characteristics of the vesicular neurotransmitter transporters(VNTs), which all belong to the DHA12 family. Two crystal structures were produced for E. coli Mdf A, one in complex with acetylcholine and the other with potential reserpine, which are substrate and inhibitor of VNTs,respectively. These structures show that the binding sites of these two molecules are different. The Achbinding Mfd A is mainly dependent on D34, while reserpine-binding site is more hydrophobic. Based on sequence alignment and homology modelling, we were able to provide mechanistic insights into the association between the inhibition and the conformational changes of these transporters.

关键词： Acetylcholine Antiporter DHA12 MdfA reserpine

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Inhibitory effects of reserpine and carbonyl cyanide m-chloro-phenylhydrazone on fluoroquinolone resistance of Acinetobacter baumannii

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Chinese Medical Journal 2005年第4期118卷 340-343页

作者： SHIWei-feng JIANGJian-ping XUNing HUANGZhi-mi WANGYu-yue DepartmentofClinicalLaboratory ThirdAffiliatedHospitalofSuzhouUniversityChangzhou213003China DepartmentofClinicalChemistry UniversityHospitalofLundLundS-22185Sweden DepartmentofClinicalLaboratory 98thPLAHospitalHuzhou313000China

Mechanisms of bacterial resistance to fluoro-quinolones may be grouped intothree principal categories: gene mutations of DNA topoisomerase Ⅱ (GyrA or GyrB), DNA topoisomeraseⅣ ( ParC or ParE), decrease of outer membrane permeation and upregulation of multi-drug effluxpump (active efflux system). Efflux pumps are transport proteins removing toxic substrates(including virtually all classes of clinically relevant antibiotics) from cells to the externalenvironment. These proteins exist in both Gram positive bacteria and Gram negative bacteria as wellas in fungi and mammalian (tumour) cells. It has been reported that alkaloid reserpine and carbonylcyanide m-chlorophenylhydrazone (CCCP) can inhibit NorA multi-drug efflux. In order to explore theuniversality of drug efflux in microorganisms, 85 strains of Acinetobacter baumannii (A. baumannii)were tested using reserpine and CCCP. The quinolone-resistant-determining region (QRDR) of gyrA andparC genes in 35 isolates of A. baumannii were amplified by polymerase chain reaction (PCR) andsequenced by DNA sequencer. The correlation between resistant mutation regularity and bacterial drugefflux were analysed.

关键词： acinetobacter baumannii efflux effect reserpine carbonyl cyanidem-chlorophenylhydrazone gyrA parC

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Brain IL-1β was involved in reserpine-induced behavioral depression in rats

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Acta Pharmacologica Sinica 2004年第3期25卷 39-42页

作者： Thomas R MINOR Bethune MilitaryMedical College China Department of Psychology Los Angeles PsychoneuroimmunolgyLaboratory Shijiazhuang 050081 USA University of California

AIM: To investigate the mechanism of brain interleukin-1β (IL-1β) in reserpine-induced behavioral depression in rats. METHODS: Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1β. RESULTS: Intraperitoneal injection of reserpine (0, 4, 6, and 8 mg/kg, ip) increased floating time in the Porsult swim test in a dose-and time-dependent manner in rats. Intracerebroventricular injection (icv) of IL-1β receptor antagonist (IL-1ra, 6 mg/kg) blocked the increment of floating time in Porsult swim test at 48 and 72 h after reserpine injection, but not at 1 and 24 h after injection. Brain IL-1β increased after reserpine treatment in posterior cortex, hippocampus, and hypothalamus. The increase of IL-1β concentration starts at 24 hours after injection of reserpine and reached the peak at 48 h. CONCLUSION: reserpine induced behavioral depression partially via brain interleukin-1β generation.

关键词： reserpine depression interleukin-1

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Toward Total Synthesis of Yohimbine and reserpine Alkaloids;Part 1.An Improved Synthesis of cis-5,8-Dihydroxy-1,4,5,8,9,10-hexahydronaphthalene-1,8-lactone via Selective Reduction of the Conjugated Ketone with Zn(BH_4)_2

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Chinese Chemical Letters 2004年第3期15卷 265-268页

作者： YongYeLI MeiXU FenErCHEN DepartmentofChemistry FudanUniversityShanghai200433

An improved and high-yielding synthesis of cis-5, 8-dihydroxy-1, 4, 5, 8, 9, 10- hexahydronaphthalene-1,8-lactone 7, an intermediate for (-)-reserpine 1 is presented. The conjugated ketone 5 was regioselectively reduc... 详细信息

关键词： reserpine lactone zinc borohydride reduction synthesis.

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Flow-injection Chemiluminescence Determination of reserpine in Medicine and Biological Fluids with Controlled-Reagent-Release Technology

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Chinese Journal of Chemistry 2003年第2期21卷 175-180页

作者：宋正华张尼 Department of Chemistry Northwest University Xi'an Shaanxi 710069 China

A sensitive and rapid chemiluminescence (CL) flow injection with controlled reagent release technology for the determination of reserpine was proposed. The CL reagents, luminol and dichromate, used in this sensor, were all immobilized on anion exchange resin. Through injection of 100 μL of water, the reagents on the anion exchange resin column were eluted and in the presence of reserpine, the CL intensity was decreased, by which reserpine could be sensed. reserpine was quantified by measuring the decrement of CL intensity, which was observed linear with the logarithm of reserpine concentration in the range of 1 0-500 0 ng/mL, and the limit of detection was 0 4 ng/mL (3 σ ) with a relative standard deviation of less than 3 0%. The proposed procedure was applied in the assay of reserpine in pharmaceutical preparation and biological fluids without any pre treatment process and with sampling frequencies of 72 times per hour.

关键词： reserpine flow injection chemiluminescence medicine urine

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利血平和丘脑下部促黄体素释放激素类似物(LHRH-A)对大鳞副泥鳅促性腺激素细胞的分泌活动和排卵的促进作用

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动物学报 1985年第4期34卷 313-318,390-391页

作者：林浩然彭纯刘龙志周溪涓中山大学生物学系

利血平能使神经分泌细胞的儿茶酚胺贮存量减少甚至消耗殆尽,导致多巴胺作为GRIF的作用减弱,从而显著增强LHRH-A促进GtH分泌和诱导排卵的效应。对大鳞副泥鳅,利血平和LHRH-A同时注射或者利血平比LHRH-A提前3小时注射,都能激活GtH细胞,显... 详细信息

利血平能使神经分泌细胞的儿茶酚胺贮存量减少甚至消耗殆尽,导致多巴胺作为GRIF的作用减弱,从而显著增强LHRH-A促进GtH分泌和诱导排卵的效应。对大鳞副泥鳅,利血平和LHRH-A同时注射或者利血平比LHRH-A提前3小时注射,都能激活GtH细胞,显著增强其分泌活动并诱导排卵。利血平的最低有效剂量为1—5微克/克体重。利血平(25微克/克体重)+LHRH-A(0.05微克/克体重)的催产效果和多巴胺拮抗物pimozide(1微克/克体重)+LHRH-A(0.05微克/克体重)的催产效果一样,排卵率都达到了100％。

关键词： reserpine LHEH-A Ovulation Gonadotropin Gonadotrops Loach.

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