DOCSLIB.ORG

Pjp3'2003 Symp.Vp:Corelventura

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pjp3'2003 Symp.Vp:Corelventura THIRTY YEARS OF COOPERATION BETWEEN GERMAN AND POLISH PHARMACOLOGISTS. NEW PERSPECTIVES IN THE COMMON EUROPE Pharmacology is only just a small part of the science and scientists are a small fraction of each country. However, the example of joint activities of Polish and German pharmacologists shows that making new human relationships is possible. Jerzy Maj n Official Symposium of the Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie and of the Polish Pharmacological Society n Białowieża, September 18–21, 2003 ENDOGENOUS 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES POSSESS ANTIDOPAMINERGIC AND NEUROPROTECTIVE ACTIVITY IN RAT BRAIN Lucyna Antkiewicz-Michaluk, Jerzy Michaluk, Irena Romañska, Andrzej Bojarski, Jerzy Vetulani Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smêtna 12, PL 31-343 Kraków, Poland 1,2,3,4-Tetrahydroisoquinoline derivatives (TIQs) on both pathways of DA catabolism, inhibition of are present both in man and animal brain, and may MAOB-dependent N-oxidation, and acceleration at play important physiological role. However, the least twice the COMT-dependent O-methylation. earlier studies have suggested neurotoxic effect of Such an effect on DA catabolism may reduce the TIQs, resulting from their similarity to 1-methyl- generation of free radicals accompanying this pro- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and cess. We also investigated whether 1MeTIQ exerts ability to form tetrahydroisoquinolinium ions, ana- a protective action against the degeneration of do- logous to 1-methyl-4-phenylpyridinium ion (MPP+), paminergic terminals induced by neurotoxic herbi- and in fact experimental parkinsonism was induced cide – rotenone (7 days, 10 mg/kg sc) in rat brain. by TIQs (TIQ, salsolinol, 1-BnTIQ) in rodents and We have found that repeated but not single admini- marmosets [1, 2]. Another TIQ derivative – 1-me- stration of rotenone causing abnormalities in ge- thyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) – neral behavior of rats, produced considerable mor- was regarded as a neuroprotectant antagonizing the tality, and dramatic increases in DA metabolism, parkinsonism-like behavioral abnormalities in mice which may be ascribed to an increase in the oxida- [3]. In our study, we investigated the acute and tive pathways (strong increase in DOPAC level), chronic effect of TIQs in the behavioral and bio- and 1MeTIQ completely antagonized these effects. chemical experiments. In summary, we have demonstrated that TIQs The results have shown that all investigated tet- are the ideal candidates for natural regulators of rahydroisoquinoline compounds: TIQ, salsolinol, DA system, that would prevent its hyperactivity, 1BnTIQ and 1-MeTIQ administered to rodents and additionally the results have shown neuropro- (25–100 mg/kg ip) antagonized effectively in dose- tective activity of 1MeTIQ against rotenone-indu- related manner the behavioral action (locomotor ced neurodegeneration. hyperactivity) induced by dopamine (DA) agonists: apomorphine and amphetamine (0.25 and 0.5 mg/kg REFERENCES sc). Biochemical experiments have shown the dif- 1. ferences in effects of two tetrahydroisoquinolines: Antkiewicz-Michaluk L., Michaluk J., Mokrosz M., Romañska I., Lorenc-Koci E., Ohta S., Vetulani J.: 1MeTIQ and 1BnTIQ on DA metabolism and ca- Different action on dopamine catabolic pathways of tabolism which would explain their neuroprotec- two endogenous 1,2,3,4-tetrahydroisoquinolines with tive and neurotoxic ability. 1MeTIQ did not change similar antidopaminergic properties. J. Neurochem., the DA concentration either after acute or chronic 2001, 78, 100–108. treatment in any investigated structures (substantia 2. Nagatsu T., Yoshida M.: An endogenous substance of nigra, striatum, nucleus accumbens). In contrast, the brain, tetrahydroisoquinoline, produces parkinson- ism in primates with decreased dopamine, tyrosine hy- 1BnTIQ produced a dramatic fall of DA level in droxylase and biopterin in the nigrostriatal region. the striatum and nucleus accumbens with the in- Neurosci. Lett., 1988, 87, 178–182. crease in homovanillic acid level (HVA), which in- 3. Tasaki Y., Makino Y., Ohta S., Hirobe M.: 1-Methyl- dicates a massive release of DA from the nerve 1,2,3,4-tetrahydroisoquinoline, decreasing in 1-methyl- endings. This effect may be the cause of neurotoxic 4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse, pre- properties of 1BnTIQ. The neuroprotective action vents parkinsonism-like behavior abnormalities. J. Neu- of 1MeTIQ may be explained by its different action rochem., 1991, 57, 1940–1943. ISSN 1230-6002 479 Abstracts of Symposium EFFECTS OF FELBAMATE AND ITS COMBINATIONS WITH CONVENTIONAL ANTIEPILEPTIC DRUGS IN AMYGDALA-KINDLED RATS Kinga K. Borowicz, Stanis³aw J. Czuczwar Department of Pathophysiology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland Felbamate modified behavioral and electro- doses of valproate, phenobarbital, diphenylhydan- graphic correlates of kindled seizures in rats. In de- toin or clonazepam did not express any protective tail, when applied at the dose of 5 or 10 mg/kg, action. The concomitant treatment of felbamate felbamate significantly increased afterdischarge with conventional antiepileptics did not induce threshold, shortened seizure and afterdischarge du- any significant motor impairment in the chimney rations, but remained without effect on seizure se- test or memory deficit in the passive avoidance verity. Furthermore, the combination of felbamate task. A pharmacokinetic interaction between felba- (2.5 mg/kg) with carbamazepine (7.5 mg/kg; both mate and carbamazepine can be excluded, at least drugs at their subeffective doses), reduced the sei- at the level of plasma and brain concentrations. The zure severity and afterdischarge duration of kindled antiseizure efficacy of felbamate/carbamazepine seizures. In respect of afterdischarge duration, the combination evaluated in the present study may antiseizure potency of the felbamate/carbamaze- justify its usage as an add-on therapy, being worth pine combination was comparable to that of carba- considering particularly in cases of multiple drug- mazepine alone administered at 10 mg/kg. Neither resistant partial epilepsy. carbamazepine (7.5 and 10 mg/kg) nor felbamate (2.5–10 mg/kg) affected seizure severity, whereas REFERENCES combined treatment of felbamate (2.5 mg/kg) with 1. Borowicz K.K., Stasiuk G., Teter J., Kleinrok Z., carbamazepine (7.5 mg/kg) led to significant re- G¹sior M., Czuczwar S.J.: Low propensity of conven- duction of seizure severity from 5th to 3rd stage of tional antiepileptic drugs for interaction with felba- Racine’s scale. Among conventional antiepileptic mate against maximal electroshock-induced seizures in mice. J. Neural Transm., 2000, 107, 733–743. drugs tested in this study, only valproate (100 2. Ebert U., Reissmüller E., Löscher W.: The new antie- mg/kg) and clonazepam (0.1 mg/kg) exerted simi- pileptic drugs lamotrigine and felbamate are effective lar action on seizure severity. However, the combi- in phenytoin-resistant kindled rats. Neuropharmacolo- nations of felbamate (2.5 mg/kg) with subeffective gy, 2000, 39, 1893–1903. EFFECT OF CYCLOOXYGENASE AND NITRIC OXIDE SYNTHASE INHIBITORS ON ANTINOCICEPTIVE ACTION OF ACETAMINOPHEN Magdalena Bujalska Department of Pharmacodynamics, Medical University, Krakowskie Przedmiecie 26/28, PL 00-927 Warszawa, Poland Acetaminophen (ACETA), an active metabolite from those of aspirin (ASA), this drug has widely of phenacetin, is a commonly used antinocicep- replaced ASA and other salicylates in the treatment tive/antypyretic drug. Although its antinociceptive of mild to moderate pain in conditions not associ- and antipyretic activities do not differ markedly ated with inflammatory processes such as head- 480 Pol. J. Pharmacol., 2003, 55, 479–518 THIRTY YEARS OF COOPERATION BETWEEN GERMAN AND POLISH PHARMACOLOGISTS ache, toothache and dysmenorrhoea. A lack of anti- hibitor preferentially acting on COX-1, as well as inflammatory activity can be attributed to the fact nimesulide (NIM) and celecoxib (CECOX), prefer- that ACETA does not influence or does not sub- ential and selective inhibitor of COX-2 respec- stantially inhibit the activity of cyclooxygenases tively, administered, icv or peripherally almost (COXs) in peripheral tissues [1, 2]. completely blocked the antinociceptive effect of In spite of the numerous investigations, the ACETA in Randall-Selitto method. On the other mechanism of ACETA action is still poorly defined hand, pretreatment with NSAIDs it initially in- and has been not satisfactorily explained. creased and then attenuated the ACETA antinoci- It was, therefore, of interest to investigate the ception. Yohimbine did not modify antinociceptive effects of COX and nitric oxide synthase (NOS) in- action of ACETA when administered alone. How- hibitors on the antinociceptive activity of ACETA. ever, yohimbine decreased the nociceptive threshold Effect of yohimbine, an a2-adrenergic receptor an- increased by co-administration of IND and ACETA, tagonist, was also checked. NIM and ACETA as well as CECOX and ACETA Intrathecal (it), intracerebroventricular (icv)or in Randall-Selitto model. peripheral pretreatment with L-G-nitro-L-arginine The results of this study indicate that both COX (L-NO-Arg), a non-selective inhibitor of NOS ac- and nNOS systems are involved in the antinocicep- tivity, as well as with 7-nitroindazole (7-NI), an se- tive activity of ACETA. lective inhibitor of neuronal NOS,
Load more

Recommended publications
  • Chiral CE Separation of Dopamine-Derived Neurotoxins
    ANALYTICAL SCIENCES FEBRUARY 2005, VOL. 21 115 2005 © The Japan Society for Analytical Chemistry Chiral CE Separation of Dopamine-Derived Neurotoxins Zhe QUAN,* Yaru SONG,* Gladys PETERS,* Ming SHENWU,* Yinghong SHENG,* Huey-Min HWANG,** and Yi-Ming LIU*† *Department of Chemistry, Jackson State University, 1400 Lynch St., Jackson, MS 39217, USA **Department of Biology, Jackson State University, 1400 Lynch St., Jackson, MS 39217, USA An enantiomeric separation of dopamine-derived neurotoxins by capillary electrophoresis has been developed. Tetrahydroisoquinoline (TIQ), dopamine (DA), (R/S)-1-benzyl-TIQ (BTIQ), (R/S)-6,7-dihydroxy-1-methyl-TIQ (salsolinol, Sal), and (R/S)-6,7-dihydroxy-1, 2-dimethyl-TIQ (N-methyl-salsolinol, NMSal) were studied as model compounds. The CE running buffer (50 mM phosphate buffer at pH 3.0) contained 1.5 M urea and 12 mM β-CD as a chiral selector. During separation, the (R)-enantiomers formed more stable inclusion complexes with β-CD, and thus had a longer migration time than their optical antipodes. It was noticed that the recovery rates of these TIQ derivatives were very poor (< 15%) during protein precipitation, a procedure widely used for cleaning up biological samples. The recovery was significantly improved by pre-mixing the sample with a surfactant (e.g., sodium hexanesulfonate or Triton X-100) to reduce the co-precipitation. The present method in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was applied to study samples obtained from in vitro incubation of two catecholamines, dopamine and epinine, with aldehydes forming neurotoxins including (S)- and (R)-NMSal enantiomers. The later is known to induce Parkinsonism in rats.
    [Show full text]
  • The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines
    Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 1983 The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines Jerome James Hannigan Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Medicine and Health Sciences Commons Recommended Citation Hannigan, Jerome James, "The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines" (1983). Dissertations. 2225. https://ecommons.luc.edu/luc_diss/2225 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 1983 Jerome James Hannigan The Neurochemical Effects of Several Carboxylated Tetrahydroisoquinolines by Jerome James Hannigan A Dissertation Submitted to the Faculty of the Graduate School of Loyola University of Chicago. in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY June 1983 .,.. ·-. ~ 1983, Jerome James Hannigan ACKNOWLEDGEMENTS I would like to acknowledge Dr. Michael Collins for his role in training me to be a research scientist. His supervision has been helpful in pursuing the answers to the questions addressed by this dissertation. I wish to thank Dr. Byron Anderson for encouraging me to pursue a career in Biochemistry. I have come to share his love for science. I could not have survived graduate school without the help and guidance of the faculty of the Department of Biochemistry. To my fellow students I owe a debt of gratitude.
    [Show full text]
  • Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression
    Molecules 2014, 19, 20864-20879; doi:10.3390/molecules191220864 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression Yousef Tizabi *, Laura L. Hurley, Zakiya Qualls and Luli Akinfiresoye Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA; E-Mails: [email protected] (L.L.H.); [email protected] (Z.Q.); [email protected] (L.A.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-202-806-9719, Fax: +1-202-806-4453. External Editors: Sahdeo Prasad and Bharat B. Aggarwal Received: 21 October 2014; in revised form: 5 December 2014 / Accepted: 8 December 2014 / Published: 12 December 2014 Abstract: This review is an attempt to summarize our current understanding of curcumin’s potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed co-morbid conditions of a neurodegenerative and a neuropsychiatric disorder. Moreover, in line with the theme of this series, the role of inflammation and stress in these diseases and possible anti-inflammatory effects of curcumin, as well as its interaction with signal transduction proteins as a common denominator in its varied mechanisms of action, are also discussed. Thus, following a brief introduction of curcumin’s pharmacology, we present research suggesting how its anti-inflammatory properties have therapeutic potential in treating a devastating neurological disorder (Parkinson’s disease = PD) and a debilitating neuropsychiatric disorder (major depressive disorder = MDD).
    [Show full text]
  • Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2008 Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification Satjit Singh Brar Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/902 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Satjit Singh Brar 2008 All Rights Reserved EFFECTS OF SMOKING AND GENDER ON TETRAHYDROISOQUINOLINES AND β–CARBOLINES IN A HEALTHY POPULATION AND DURING ALCOHOL DETOXIFICATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by SATJIT SINGH BRAR B.S., University of California at Santa Barbara, 1998 Director: Jürgen Venitz, MD, Ph.D. Associate Professor, Department of Pharmaceutics Virginia Commonwealth University Richmond, Virginia May 2008 ii Acknowledgements Jürgen Venitz, first and foremost, for giving me the opportunity to pursue graduate studies under his guidance. His mentoring in academics and research has been truly motivating and inspirational. Members of my graduate committee, Drs. Jürgen Venitz, John Rosecrans, Patricia Slattum, Vijay Ramchandani, H. Thomas Karnes, and Hee-Yong Kim for their efforts, patience and time for serving on my committee. Patricia Slattum for her advice and encouragement. She has provided valuable aid over the years by giving guidance throughout my tenure in the Pharm.D./Ph.D.
    [Show full text]
  • On Dopamine Secretion and Its Intracellular Dynamics in Rat Pheochromocytoma PC 12 Cells
    Effects of an endogenous dopaminergic neurotoxin, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol), on Title dopamine secretion and its intracellular dynamics in rat pheochromocytoma PC 12 cells Author(s) MARUYAMA, Yutaka Citation Japanese Journal of Veterinary Research, 49(1), 47-48 Issue Date 2001-05-31 Doc URL http://hdl.handle.net/2115/2878 Type bulletin (article) File Information KJ00002400340.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Jpn. J. Vet. Res. 49 ( 1 ), (2001) Information 47 Effects of an endogenous dopaminergic neurotoxin, 6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline (norsalsolinoO, on dopamine secretion and its intracellular dynamics in rat pheochromocytoma PC 12 cells Yutaka Maruyama Laboratory of Toxicology Department of Environmental Veterinary Sciences Graduate School of Veterinary Medicine Hokkaido University, Sapporo 060-0818, Japan Naturally occurring neurotoxins, 6, 7- (vmax) of 55. 6 ± 3. 5 pmollminJrng protein (n dihydroxy-1, 2, 3, 4 -tetrahydroisoquinolines = 4 ). The uptake of norsalsolinol was sensi­ (DHTIQs), have been thought to be the tive to two dopamine transporter (DAT) in­ causative agents of parkinsonism. DHTIQs, hibitors, GBR-12909 and reserpine, but was including norsalsolinol, have been found in less sensitive to desipramine, a noradrenaline the mammalian central nervous system. Nor­ transporter inhibitor. Dopamine, an endoge­ salsolinol can be formed in parkinsonian pa­ nous DAT substrate, inhibited norsalsolinol tients. However, the effects of DHTIQs on the uptake into PC 12 cells. The Km and Vmax secretion of dopamine, as well as other neuro­ values of the uptake of norsalsolinol in the transmitters, have not been elucidated. In presence of 100 11M dopamine were 241.
    [Show full text]
  • Inhibition of Rodent Brain Monoamine Oxidase and Tyrosine Hydroxylase by Endogenous Compounds – 1,2,3,4-Tetrahydroisoquinoline Alkaloids
    Copyright © 2004 by Institute of Pharmacology Polish Journal of Pharmacology Polish Academy of Sciences Pol. J. Pharmacol., 2004, 56, 727734 ISSN 1230-6002 INHIBITION OF RODENT BRAIN MONOAMINE OXIDASE AND TYROSINE HYDROXYLASE BY ENDOGENOUS COMPOUNDS – 1,2,3,4-TETRAHYDROISOQUINOLINE ALKALOIDS Antoni Patsenka, Lucyna Antkiewicz-Michaluk Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smêtna 12, PL 31-343 Kraków, Poland Inhibition of rodent brain monoamine oxidase and tyrosine hydroxylase by endogenous compounds – 1,2,3,4-tetrahydroisoquinoline alkaloids. A. PATSENKA, L. ANTKIEWICZ-MICHALUK. Pol. J. Pharmacol., 2004, 56, 727–734. Four different noncatecholic and one catecholic tetrahydroisoquinolines (TIQs), cyclic condensation derivatives of b-phenylethylamine and dopa- mine with aldehydes or keto acids, were examined for the inhibition of rat and mouse brain monoamine oxidase (MAO) and rat striatum tyrosine hy- droxylase (TH) activity. Simple noncatecholic TIQs were found to act as moderate (TIQ, N-methyl-TIQ, 1-methyl-TIQ) or weak (1-benzyl-TIQ), MAO B and MAO A inhibitors. 1-Methyl-TIQ inhibited more potently MAO-A than MAO-B; the similar but more modest effect was exerted by salsolinol. Only salsolinol markedly inhibited TH activity, being competitive with the enzyme biopterin cofactor. The inhibition of MAO and TH by TIQs is discussed in relation to their ability to regulate monoamine metabolism. Key words: monoamine oxidase, tyrosine hydroxylase, inhibition of en- zyme activity, tetrahydroisoquinoline derivatives correspondence; e-mail: [email protected] A. Patsenka, L. Antkiewicz-Michaluk Abbreviations: BBB – blood-brain barrier,BH" been found to be toxic to dopaminergic neurons – 5,6,7,8-tetrahydrobiopterin, CSF – cerebrospinal and their concentration has been shown to increase fluid, 5-HT – 5-hydroxytryptamine, MAO – mono- in parkinsonian brains or cerebrospinal fluid (CSF) amine oxidase, MPTP – 1-methyl-4-phenyl-1,2,3,6- [12].
    [Show full text]
  • HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits
    cells Review HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits Kristen A. McLaurin †, Michael Harris †, Victor Madormo †, Steven B. Harrod, Charles F. Mactutus and Rosemarie M. Booze * Department of Psychology, University of South Carolina, Columbia, SC 29208, USA; [email protected] (K.A.M.); [email protected] (M.H.); [email protected] (V.M.); [email protected] (S.B.H.); [email protected] (C.F.M.) * Correspondence: [email protected] † These authors contributed equally. Abstract: Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 Citation: McLaurin, K.A.; Harris, M.; seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, Madormo, V.; Harrod, S.B.; Mactutus, C.F.; Booze, R.M. HIV-Associated the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit Apathy/Depression and observed following chronic HIV-1 viral protein exposure.
    [Show full text]
  • A Secret That Underlies Parkinson's Disease the Damaging Cycle
    Neurochemistry International 129 (2019) 104484 Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint A secret that underlies Parkinson's disease: The damaging cycle T Feiyi Suna, Yulin Denga, Xiaowei Hanb,c, Qingqing Liua,1, Peng Zhanga, Robina Manzoora, ∗ Hong Maa, a School of Life Science, Beijing Institute of Technology, Beijing, 100081, China b Department of Radiology, Heping Hospital Affiliated with Changzhi Medical College, Changzhi, 046000, China cGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, 100730, China ARTICLE INFO ABSTRACT Keywords: Parkinson's disease (PD) is a movement disorder, and its common characteristics include the loss of dopami- Parkinson's disease nergic neurons and the accumulation of a special type of cytoplasmic inclusions called Lewy bodies in the Oxidative stress substantia nigra pars compacta, which are more prevalent in the elderly. However, the pathophysiology of PD is Endogenous neurotoxins still elusive. In this review, we summarized five common factors involved in PD, namely, (i) oxidative stress, (ii) Inflammation mitochondrial dysfunction, (iii) inflammation, (iv) abnormal α-synuclein, and (v) endogenous neurotoxins, and α-Synuclein aggregation proposed a hypothesis involving a damaging cycle. Oxidative stress-triggered aldehydes react with biogenic Damaging cycle amines to produce endogenous neurotoxins. They cause mitochondrial dysfunction and the formation of in- flammasomes, which induce the activation of neuroglial cells and the infiltration of T lymphocytes. Thesy- nergistic effect of these processes fosters chronic inflammation and α-synuclein aggregation and furtherex- acerbates the impact of oxidative stress to establish a damaging cycle that eventually results in the degeneration of dopaminergic neurons.
    [Show full text]
  • Recent Advances in Mass Spectrometry for the Identification of Neuro-Chemicals and Their Metabolites in Biofluids
    Send Orders for Reprints to [email protected] 436 Current Neuropharmacology, 2013, 11, 436-464 Recent Advances in Mass Spectrometry for the Identification of Neuro- chemicals and their Metabolites in Biofluids Suresh Kumar Kailasaa and Hui-Fen Wub,c,d,e,* aDepartment of Applied Chemistry, S. V. National Institute of Technology, Surat – 395007, India; bDepartment of Chemistry, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan; cSchool of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 800, Kaohsiung, Taiwan; dCenter for Nanoscience and Nanotechnology, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan; eDoctoral Degree Program in Marine Biotechnology, National Sun Yat- Sen University, Kaohsiung 80424, Taiwan Abstract: Recently, mass spectrometric related techniques have been widely applied for the identification and quantification of neurochemicals and their metabolites in biofluids. This article presents an overview of mass spectrometric techniques applied in the detection of neurological substances and their metabolites from biological samples. In addition, the advances of chromatographic methods (LC, GC and CE) coupled with mass spectrometric techniques for analysis of neurochemicals in pharmaceutical and biological samples are also discussed. Keywords: Neurochemicals, LC-MS, GC-MS, CE-MS, MALDI-MS. INTRODUCTION medical examinations. Few drugs (TCAs) inhibit the reuptake of norepinephrine (desipramine, nortriptyline, and Neuroscience is the subject to study the chemical protriptyline secondary amines) and serotonin (amitriptyline, composition and processes of the nervous system, which imipramine, clomipramine, and doxepine tertiary amines) in includes the brain, the spinal cord and the nerves and the the central nervous system [2-4]. In order to detect their effects of chemicals on them. As with all the senses, our concentration from human fluids, tandem mass spectrometry perception of outside world is processed by the peripheral has been widely used for sensitive identificaiton and and central nervous systems.
    [Show full text]
  • Salsolinol, a Derivate of Dopamine, Is a Possible Modulator of Catecholaminergic Transmission: a Review of Recent Developments
    Physiol. Res. 55: 353-364, 2006 MINIREVIEW Salsolinol, a Derivate of Dopamine, is a Possible Modulator of Catecholaminergic Transmission: a Review of Recent Developments B. MRAVEC Institute of Experimental Endocrinology, Slovak Academy of Sciences and Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic Received May 31, 2005 Accepted August 17, 2005 On-line available October 17, 2005 Summary Catecholamine (dopamine, norepinephrine and epinephrine) synthesizing neurons are widely distributed in the brain, sympathetic ganglia and throughout peripheral organs. Results of several recent experiments clearly suggest that many of these neurons can also contain 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), a derivate of dopamine. However, direct proof of salsolinol synthesis in those neurons is still missing. The data obtained with administration of exogenous salsolinol strongly indicate that it may play an important role in catecholaminergic regulatory processes, such as the regulation of prolactin release and/or neuronal transmission in sympathetic ganglia. Several recent data have also indicated a relationship between salsolinol or its metabolites and the etiology of Parkinson's disease or neuropathology of chronic alcoholism. These seemingly different roles of salsolinol will be discussed separately, but some common features will also be highlighted. Based on all of the discussed data the existence of a “salsolinolergic” system using salsolinol as a neuromodulator, which may be present in catecholamine synthesizing neurons, is postulated. Key words Salsolinol • Dopamine • Prolactoliberin • Parkinson’s disease • 1MeDIQ Introduction Nobel Prize in 2000 (Carlsson 2001). The brain dopaminergic system is implicated in a variety of The neurotransmitters dopamine, norepinephrine physiological and pathophysiological processes.
    [Show full text]
  • Altered Urinary Tetrahydroisoquinoline Derivatives in Patients with Tourette Syndrome: Reflection of Dopaminergic Hyperactivity?
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2021 Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity? Capetian, Philipp ; Roessner, Veit ; Korte, Caroline ; Walitza, Susanne ; Riederer, Franz ; Taurines, Regina ; Gerlach, Manfred ; Moser, Andreas Abstract: Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neuro- transmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017).
    [Show full text]
  • Increased Systemic Levels of Norsalsolinol Derivatives Are
    634 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2003.010769 on 16 March 2004. Downloaded from SHORT REPORT Increased systemic levels of norsalsolinol derivatives are induced by levodopa treatment and do not represent biological markers of Parkinson’s disease J Scholz, I Klingemann, A Moser ............................................................................................................................... J Neurol Neurosurg Psychiatry 2004;75:634–636. doi: 10.1136/jnnp.2003.010769 6,7-dihydroxylated tetrahydroisoquinolines might be a con- Endogenously synthesised norsalsolinol derivatives are ele- sequence of therapeutically administered levodopa (L-dopa), vated in Parkinson’s disease (PD) and have been considered which is subsequently decarboxylated to dopamine.8–10 potentially useful biological markers of the disease. However, However, this issue has not been studied directly. little is known about the impact of dopaminergic drugs on the We prospectively measured urine levels of Norsal, formation of these compounds. We prospectively examined NMnorsal, and salsolinol in PD patients and control subjects. the urine concentrations of norsalsolinol, N-methyl-norsal- Individuals were examined again after approximately one solinol and salsolinol in 47 PD patients and 14 control year. Our objective was to determine whether systemic subjects. Patients and control subjects were re-examined after concentrations of Norsal derivatives represent useful biologi- approximately 1 year to assess long term changes. cal markers
    [Show full text]