DOCSLIB.ORG

1469.Full.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1469.Full.Pdf [CANCER RESEARCH 41, 1469-1482, April 1981) 0008-5472/81 /0041-OOOOS02.00 DMA-damaging Activity in Vivo and Bacterial Mutagenicity of Sixteen Hydrazine Derivatives as Related Quantitatively to their Carcinogenicity1 Silvio Parodi, Silvio De Flora, Marco Cavanna, Albiana Pino, Luigi Robbiano, Carlo Bennicelli, and Giovanni Brambilla2 Departments of Pharmacology [M. C.. A. P., L. P., G. B.¡,Hygiene [S. D. F., C. B.]. and Oncology [S. P.¡,Genoa University. 16132 Genoa, Italy ABSTRACT enees existing in the carcinogenic potency of different chemi cals, qualitative statements of positivity or negativity in a short- Sixteen hydrazine derivatives (hydrazine, 1,1-dimethylhydra- term test are of very limited value for an assessment of the zine, 1,2-dimethylhydrazine, phenylhydrazine, procarbazine, carcinogenic risk. isoniazid, isocarboxazid, nialamide, 2,4-dinitrophenylhydra- In this work, we attempted a quantitative comparison of the zine, phenelzine, hydralazine, dihydralazine, carbamylhydra- potencies of 16 hydrazine derivatives in: (a) inducing DNA zine, mebanazine, iproniazid, and 1-carbamyl-2-phenylhydra- fragmentation in liver and lung of male Swiss mice, as evaluated zine) were tested for DNA-damaging activity by the alkaline by alkaline elution technique; (b) inducing mutations in the elution technique and for mutagenic activity in the Salmonella- Sa/mone/te-microsome test, both in the presence and in the microsome (Ames) test. The first nine compounds listed (56%) absence of S-9 mix; and (c) inducing pulmonary tumors in were found to induce a significant DNA fragmentation in the chronically treated mice. The significance of a quantitative liver and/or in the lung of i.p.-treated male Swiss mice. The comparison is probably strongly dependent on the internal DNA-damaging potency varied over an ~30-fold range. Thir homogeneity of the sets of experiments that are compared. In teen of the first 14 compounds listed (81% of the total), this respect, the hydrazine derivatives appeared a rather con isocarboxazid being inactive, were positive in the Ames test, venient family of chemical compounds because their carcino with a broad range of activity towards the five bacterial strains genicity was studied mainly by a single group of investigators of Salmonella typhimurium used (TA1535, TA100, TA1537, according to a fixed protocol (42). Moreover, the carcinogenic TA1538, and TA98) and of metabolic behavior in the presence potencies of the hydrazine derivatives tested vary over a 1900- of S-9 mix containing rat liver, mouse liver, or mouse lung fold range, which seems to be a sufficiently large interval to postmitochondrial preparations from Aroclor-treated animals. allow for quantitative comparisons. The internal homogeneity The mutagenic potency varied over an almost 7000-fold range. of DNA damage and of mutagenicity data should be assured For 11 of the 16 hydrazine derivatives tested, homogeneous by the fact they were both directly obtained by our group in carcinogenicity data (induction of pulmonary tumors in mice experiments performed always according to the same experi chronically treated p.o.) were available from literature. Elabo mental protocol. Moreover, the 2 types of short-term tests allow ration of these data showed that carcinogenic potency varied for an additional interesting comparison: differences related to over an ~ 1900-fold range. The five most potent carcinogens in vitro versus in vivo metabolic activation. were all positive in the DNA damage test. Their carcinogenic potency varied over a 130-fold range and their DNA-damaging potency varied over a 22-fold range. DNA-damaging potency MATERIALS AND METHODS seemed to vary on a more compressed scale, but regression Chemicals analysis indicated the existence of a strong positive correlation between in vivo DNA-damaging and carcinogenic potencies, The name, structural formula, molecular weight, LD503 for while a lack of correlation was found between mutagenic and single i.p. administration in mice, source, and chemical purity carcinogenic potencies. There was no correlation between of the 16 hydrazine derivatives investigated are reported in DNA-damaging and mutagenic potencies. Table 1. Tetraethylammonium hydroxide was purchased from E. Merck, Darmstadt, West Germany; 3,5-diaminobenzoic acid INTRODUCTION dihydrochloride was obtained from Fluka AG, Buchs, Switzer land; dimethyl sulfoxide was purchased from BDH Chemicals, It has been repeatedly suggested that both induction of DNA Ltd., Poole, England. All other chemicals were reagent grade. damage in mammalian cells, measured as single-strand breaks (4, 10, 27, 30, 31) and mutagenicity in the Salmonella-micro- DNA Damage in 1/jVo-Alkaline Elution Assay some test (23, 24, 32, 33, 38) are, at least qualitatively, The in vivo assay of DNA damage was performed in non- correlated with carcinogenic activity. In recent years, however, it has become evident that, because of the tremendous differ- inbred male Swiss albino mice (aged 2 to 3 months) according to the following standardized protocol. Each hydrazine deriva 1 This work was supported by grants from the Consiglio Nazionale delle tive was tested at the following dosage schedules: (a) single Richerche (Progetto Finalizzato "Controllo della Crescita, Neoplastica"; Con i.p. administration of LD60 twice, reduced to LD60 (or one-half tracts 78.02856.96, 78.02803.96, and 79.00621.96). 2 To whom requests for reprints should be addressed, at Istituto di Farmacol of the LD50) if necessary because of lethal effect within 6 hr (or ogia dell'Università , Viale Benedetto XV, 2, 1-16132 Genoa, Italy. Received March 27. 1980; accepted October 16, 1980. 3 The abbreviation used is LDso, median lethal dose. APRIL 1981 1469 Downloaded from cancerres.aacrjournals.org on October 4, 2021. © 1981 American Association for Cancer Research. 1Hydrazines testedStructural NameHydrazine M.W.H2N-NH2-H20formula purity98% hydrate 50.1 AG, Buchs, Switzer pure land 1,1-Dimethylhydrazine1 60.1CH3-NH-NH-CH3CH3x 12595' Fluka AG, Buchs, Switzer 95-98%pure98% landE. ,2-Dimethylhydrazine-2HCI -2HCI 133.0 Merck, Darmstadt, West pure Germany Carbamylhydrazine H2N-NH-CO-NH2 75.1 123170'SourceFlukaICN-K & K Laboratories, 95-99% pure Plainview, N. Y. PhenylhydrazineTable /=\ 108.1LO»"(mg/kg)156'Carlo Erba, Milan. ItalyChemical Reagent grade 1-Carbamyl-2-phenylhydrazine 151.2 198 ' Carlo Erba, Milan, Italy Reagent grade ¿ ^-NH-NH —CO-NH2 2,4-Oinitrophenylhydrazine 198.1 450' J. T. Baker Chemicals N. V., Reagent grade Deventer, Holland o-Phenylethylhydrazine oxalate 226.2 138' Imperial Chemical Indus 98% pure (mebanazine) CH-CH3 OXALATE tries, Cheshire, Great Britain /3-Phenylethylhydrazine •H2SO4 234.3 168 W. R. Warner & Co., Pharmaceutical grade (phenelzine) //-2- CH-NH-NH2 •H2S Eastleigh, Hampshire, Great Britain W-lsopropyl-a-<2- CO-NH-CH(CH3)2 257.8 800' Hoffmann-La Roche & Co., 98.5% pure methylhydrazino)-p-toluamide • Basel, Switzerland HCI (procarbazine) •HCI CH2- NH-NH—CH3 Isonicotinic acid hydrazide (isonia- 137.1 132 Vecchi & C. Piam. Genoa, 98% pure zid) Italy 0CO-NH—NH Isonicotinic acid 2-isopropylhydra- 179.2 640 Hoffmann-La Roche & Co., 99% pure zide (iproniazid) Basel, Switzerland 0CO-NH-NH-CHCCH3)2 Isonicotinic acid 2- 298.4 435 Pfizer Italiana, Rome, Italy Pharmaceutical grade [2(benzylcarbamoyl)ethyl]hydra- zide (nialamide) CO—NH-NH - (CH)- CO—NH-CH 5-Methyl-3-isoxazolecarboxylic 231.2 49 Hoffmann-La Roche & Co., 98.5% pure acid 2-benzylhydrazide (¡socar- Basel, Switzerland boxazid) 'CO—NH-NH — 1-Hydrazinophthalazine-HCI (hy- NH - NH, 196.7 83 Ciba-Geigy, Basel, Switzer- Pharmaceutical grade dralazine) land 1,4-Dihydrazinophthalazine •H2SO4 288.3 159 Ciba-Geigy, Basel, Switzer- Pharmaceutical grade (dihydralazine) land NH - NH, 3 LDso after single i.p. administration in mice. LDso's followed by asterisk were determined as described in "Materials and Methods" in male Swiss mice. All other LDso's were obtained from Ref. 34. 1470 Downloaded from cancerres.aacrjournals.org on October 4, 2021. © 1981 American Association for Cancer Research. DNA Damage, Mutagenicity, and Carcinogenicity of Hydrazines 24 hr) from treatment; and (b) daily i.p. administration for 5 where V is the eluted volume in ml. As a first approximation, K (and sometimes 15) successive days of one-third of the LD50, is directly proportional to the number of single-strand breaks reduced to one-sixth of the LD50 or one-twelfth of the LD50 if (19). Controls were grouped into subsets of 20 experiments necessary because of lethal effects. each, which were carried out in a time interval of 3 to 4 weeks, The LDso's in mice for a single i.p. injection were as reported using the same batch of solutions for alkaline elution. The in the literature (34). When the LD50 was unknown, it was elution procedure remained unvaried for the whole period in determined at 10 days by administering i.p. to groups of 5 male which all the experiments were carried out; notwithstanding, mice for each dose a series of doses increasing serially by a some variability was observed among the various subsets of factor of 2; the LD50 was calculated (22) only after the doses controls. Consequently, the increase in DNA elution rate in given were sufficient to obtain both 0% and 100% mortality. duced by a given treatment and its statistical significance was Immediately before use, compounds soluble in water were calculated versus the subset of controls carried out approxi dissolved in 0.9% NaCI solution with small amounts of acid or mately in the same time interval. Because the distribution of alkali, if needed, to bring pH to ~7; compounds insoluble in the fractions of eluted DNA was not normal, the nonparametric water were suspended in 0.9% NaCI solution with 1% carbox- Wilcoxon 2-sample test was used for this statistical analysis ymethylcellulose as suspending agent. All compounds were (36). administered i.p. in 0.01 ml of vehicle per g of body weight. Tissue samples were taken for histológica! examination from Controls were given i.p.
Load more

Recommended publications
  • Summary of Product Characteristics
    Package leaflet: Information for the patient Fluoxetine 20mg Capsules, hard fluoxetine Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. • Keep this leaflet. You may need to read it again. • If you have further questions, ask your doctor or pharmacist. • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. •If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. What is in this leaflet 1. What Fluoxetine is and what it is used for 2. What you need to know before you take Fluoxetine 3. How to take Fluoxetine 4. Possible side effects 5. How to store Fluoxetine 6. Contents of the pack and other information 1. What Fluoxetine is and what it is used for The name of your medicine is Fluoxetine 20mg Capsules, hard. It contains the active substance fluoxetine. Fluoxetine belongs to a group of medicines called selective serotonin reuptake inhibitor (SSRI) antidepressants. Fluoxetine can be given to treat the following conditions: Adults: • Major depressive episodes • The symptoms of a condition called obsessive-compulsive disorder (OCD). • The eating disorder bulimia nervosa. This medicine is used alongside psychotherapy for the reduction of binge-eating and purging. Children and adolescents aged 8 years and above: • Moderate to severe major depressive disorder, if the depression does not respond to psychological therapy after 4-6 sessions. Fluoxetine should be offered to a child or young person with moderate to severe major depressive disorder only in combination with psychological therapy.
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Isocarboxazid Item No. 23625 CAS Registry No.: 59-63-2 Formal Name: 5-methyl-3-isoxazolecarboxylic acid, 2-(phenylmethyl)hydrazide Synonyms: NSC 169893, Ro 5-0831 H N N H MF: C12H13N3O2 FW: 231.3 N O Purity: ≥98% O Supplied as: A solid Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Isocarboxazid is supplied as a solid. A stock solution may be made by dissolving the isocarboxazid in the solvent of choice. Isocarboxazid is slightly soluble in acetonitrile and chloroform. Description 1 Isocarboxazid is an inhibitor of monoamine oxidase (MAO; IC50 = 4.8 μM for rat brain MAO). It induces a 4-fold increase in tryptamine action in isolated rat fundal strips at a concentration of 50 nM. In vivo, isocarboxazid potentiates tryptamine toxicity (LD50 = 8 mg/kg following subcutaneous administration of 250 mg/kg tryptamine). It inhibits 90% of MAO activity in isolated rat hearts and reduces cardiomegaly induced by isoproterenol (Item No. 15592) in rats at a dose of 20 mg/kg.2 Oral administration of isocarboxazid (10 mg/kg) increases levels of dopamine and norepinephrine and reduces levels of the monoamine metabolites DOPAC, homovanillic acid (HVA; Item No. 20877), and 5-hydroxy indole-3-acetic acid (5-HIAA; Item No. 22889) by 43, 32, and 28%, respectively, in mouse brain.3 Formulations containing isocarboxazid have been used for the treatment of minor depression.4 References 1. Maxwell, D.R., Gray, W.R., and Taylor, E.M. Relative activity of some inhibitors of mono-amine oxidase in potentiating the action of tryptamine in vitro and in vivo.
    [Show full text]
  • Studies on the Metabolism and Toxicity of Hydrazine in The~Rat~
    STUDIES ON THE METABOLISM AND TOXICITY OF HYDRAZINE IN THE~RAT~ Andrew Michael Jenner, B.Sc. Submitted to the University of London for the examination of the degree for Doctor of Philosophy, 1992 Toxicology Department The School of Pharmacy Brunswick Square London ProQuest Number: U068521 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest U068521 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 ACKNOWLEDGEMENTS I would like to express my sincere appreciation to my supervisor Dr. John Timbrell for his invaluable advice, guidance and support. Many people have assisted the progress of my studies in a wide variety of ways, including everyone who has worked alongside me in the Toxicology Unit, both past and present. Particular thanks go to Simon (ET) for his critical eye and mutual, down to earth Yorkshire mentality and also to Cathy for her heartening encouragement. I would also like to thank Dr. Alan Boobis for his assistance in obtaining human liver samples and to the USAF for funding this project. Finally I would like to recognise Jacqui for her designs, Maria for her typing, Justina for her continuous care and support and to my mum and dad for their understanding and my much appreciated conveyance through life.
    [Show full text]
  • Ayahuasca: Spiritual Pharmacology & Drug Interactions
    Ayahuasca: Spiritual Pharmacology & Drug Interactions BENJAMIN MALCOLM, PHARMD, MPH [email protected] MARCH 28 TH 2017 AWARE PROJECT Can Science be Spiritual? “Science is not only compatible with spirituality; it is a profound source of spirituality. When we recognize our place in an immensity of light years and in the passage of ages, when we grasp the intricacy, beauty and subtlety of life, then that soaring feeling, that sense of elation and humility combined, is surely spiritual. The notion that science and spirituality are somehow mutually exclusive does a disservice to both.” – Carl Sagan Disclosures & Disclaimers No conflicts of interest to disclose – I don’t get paid by pharma and have no potential to profit directly from ayahuasca This presentation is for information purposes only, none of the information presented should be used in replacement of medical advice or be considered medical advice This presentation is not an endorsement of illicit activity Presentation Outline & Objectives Describe what is known regarding ayahuasca’s pharmacology Outline adverse food and drug combinations with ayahuasca as well as strategies for risk management Provide an overview of spiritual pharmacology and current clinical data supporting potential of ayahuasca for treatment of mental illness Pharmacology Terms Drug ◦ Term used synonymously with substance or medicine in this presentation and in pharmacology ◦ No offense intended if I call your medicine or madre a drug! Bioavailability ◦ The amount of a drug that enters the body and is able to have an active effect ◦ Route specific: bioavailability is different between oral, intranasal, inhalation (smoked), and injected routes of administration (IV, IM, SC) Half-life (T ½) ◦ The amount of time it takes the body to metabolize/eliminate 50% of a drug ◦ E.g.
    [Show full text]
  • Dopamine: a Role in the Pathogenesis and Treatment of Hypertension
    Journal of Human Hypertension (2000) 14, Suppl 1, S47–S50 2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh Dopamine: a role in the pathogenesis and treatment of hypertension MB Murphy Department of Pharmacology and Therapeutics, National University of Ireland, Cork, Ireland The catecholamine dopamine (DA), activates two dis- (largely nausea and orthostasis) have precluded wide tinct classes of DA-specific receptors in the cardio- use of D2 agonists. In contrast, the D1 selective agonist vascular system and kidney—each capable of influenc- fenoldopam has been licensed for the parenteral treat- ing systemic blood pressure. D1 receptors on vascular ment of severe hypertension. Apart from inducing sys- smooth muscle cells mediate vasodilation, while on temic vasodilation it induces a diuresis and natriuresis, renal tubular cells they modulate sodium excretion. D2 enhanced renal blood flow, and a small increment in receptors on pre-synaptic nerve terminals influence nor- glomerular filtration rate. Evidence is emerging that adrenaline release and, consequently, heart rate and abnormalities in DA production, or in signal transduc- vascular resistance. Activation of both, by low dose DA tion of the D1 receptor in renal proximal tubules, may lowers blood pressure. While DA also binds to alpha- result in salt retention and high blood pressure in some and beta-adrenoceptors, selective agonists at both DA humans and in several animal models of hypertension. receptor classes have been studied in the treatment of
    [Show full text]
  • AHFS Pharmacologic-Therapeutic Classification System
    AHFS Pharmacologic-Therapeutic Classification System Abacavir 48:24 - Mucolytic Agents - 382638 8:18.08.20 - HIV Nucleoside and Nucleotide Reverse Acitretin 84:92 - Skin and Mucous Membrane Agents, Abaloparatide 68:24.08 - Parathyroid Agents - 317036 Aclidinium Abatacept 12:08.08 - Antimuscarinics/Antispasmodics - 313022 92:36 - Disease-modifying Antirheumatic Drugs - Acrivastine 92:20 - Immunomodulatory Agents - 306003 4:08 - Second Generation Antihistamines - 394040 Abciximab 48:04.08 - Second Generation Antihistamines - 394040 20:12.18 - Platelet-aggregation Inhibitors - 395014 Acyclovir Abemaciclib 8:18.32 - Nucleosides and Nucleotides - 381045 10:00 - Antineoplastic Agents - 317058 84:04.06 - Antivirals - 381036 Abiraterone Adalimumab; -adaz 10:00 - Antineoplastic Agents - 311027 92:36 - Disease-modifying Antirheumatic Drugs - AbobotulinumtoxinA 56:92 - GI Drugs, Miscellaneous - 302046 92:20 - Immunomodulatory Agents - 302046 92:92 - Other Miscellaneous Therapeutic Agents - 12:20.92 - Skeletal Muscle Relaxants, Miscellaneous - Adapalene 84:92 - Skin and Mucous Membrane Agents, Acalabrutinib 10:00 - Antineoplastic Agents - 317059 Adefovir Acamprosate 8:18.32 - Nucleosides and Nucleotides - 302036 28:92 - Central Nervous System Agents, Adenosine 24:04.04.24 - Class IV Antiarrhythmics - 304010 Acarbose Adenovirus Vaccine Live Oral 68:20.02 - alpha-Glucosidase Inhibitors - 396015 80:12 - Vaccines - 315016 Acebutolol Ado-Trastuzumab 24:24 - beta-Adrenergic Blocking Agents - 387003 10:00 - Antineoplastic Agents - 313041 12:16.08.08 - Selective
    [Show full text]
  • Hydrazine Sulfate Hazard Summary Identification
    Common Name: HYDRAZINE SULFATE CAS Number: 10034-93-2 RTK Substance number: 2360 DOT Number: None Date: December 1994 Revision: May 2001 ------------------------------------------------------------------------- ------------------------------------------------------------------------- HAZARD SUMMARY * Hydrazine Sulfate can affect you when breathed in and * Exposure to hazardous substances should be routinely may be absorbed through the skin. evaluated. This may include collecting personal and area * Hydrazine Sulfate should be handled as a air samples. You can obtain copies of sampling results CARCINOGEN—WITH EXTREME CAUTION. from your employer. You have a legal right to this * Hydrazine Sulfate can irritate and burn the eyes and skin. information under OSHA 1910.1020. * Breathing Hydrazine Sulfate can irritate the nose, throat * If you think you are experiencing any work-related health and lungs causing coughing and shortness of breath. problems, see a doctor trained to recognize occupational * Exposure can cause you to feel dizzy and lightheaded. diseases. Take this Fact Sheet with you. Higher levels can cause trembling, a feeling of excitement, and even convulsions (fits). WORKPLACE EXPOSURE LIMITS * Hydrazine Sulfate may damage blood cells causing a low No occupational exposure limits have been established for blood count (anemia). Hydrazine Sulfate. This does not mean that this substance is * Exposure may damage the liver and kidneys. not harmful. Safe work practices should always be followed. * Hydrazine Sulfate may cause a skin allergy. If allergy develops, very low future exposure can cause itching and a * Hydrazine Sulfate may be a CARCINOGEN in humans. skin rash. There may be no safe level of exposure to a carcinogen, so all contact should be reduced to the lowest possible level.
    [Show full text]
  • Hypertensive Crises 8.25
    Hypertensive Crises 8.25 Hypertension crises secondary to monoamine oxidase inhibitor–tyramine interactions Monoamine oxidase inhibitor therapy Impaired degradation of intracellular amines Ingestion of (epinephrine, norepinephrine, dopamine) tyramine-containing food Accumulation of catecholamines in Hepatic monamine nerve terminal storage granules oxidase inhibition with decreased Increased circulating oxidative metabolism tyramine level of tyramine Massive release of catecholamines Tachyarrhythmias Vasoconstriction (increased systemic vascular resistance) Severe paroxysm of hypertension Hypertensive encephalopathy Acute hypertensive heart failure with pulmonary edema Intracerebral hemorrhage (Fig. 8-21) (Figs. 8-24 and 8-25) FIGURE 8-32 Hypertensive crises secondary to monoamine oxidase inhibitor–tyramine interactions. Severe paroxysmal hypertension complicated by intracerebral or subarachnoid hemorrhage, hypertensive encephalopathy, or acute hypertensive heart failure can occur in patients treated with monoamine oxidase (MOA) inhibitors after ingestion of certain drugs or tyramine- containing foods [48,49]. Because MAO is required for degradation of intracellular amines, including epinephrine, norepinephrine, and dopamine, MAO inhibitors lead to accumulation of catecholamines within storage granules in nerve terminals. The amino acid tyramine is a potent inducer of neurotransmitter release from nerve terminals. As a result of inhibition of hepatic MAO, ingested tyramine escapes oxidative degradation in the liver. In addition, the high circulating levels of tyramine provoke massive catecholamine release from nerve terminals, resulting in vasoconstriction and a paroxysm of severe hypertension. A hyper- adrenergic syndrome resembling pheochromocytoma then ensues. Symptoms include severe pounding headache, flushing or pallor, profuse diaphoresis, nausea, vomiting, and extreme prostration. The mean increase in blood pressure is 55 mm Hg systolic and 30 mm Hg diastolic [49]. The duration of the attacks varies from 10 minutes to 6 hours.
    [Show full text]
  • The Effects of Phenelzine and Other Monoamine Oxidase Inhibitor
    British Journal of Phammcology (1995) 114. 837-845 B 1995 Stockton Press All rights reserved 0007-1188/95 $9.00 The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver 12 imidazoline-preferring receptors Regina Alemany, Gabriel Olmos & 'Jesu's A. Garcia-Sevilla Laboratory of Neuropharmacology, Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, E-07071 Palma de Mallorca, Spain 1 The binding of [3H]-idazoxan in the presence of 106 M (-)-adrenaline was used to quantitate 12 imidazoline-preferring receptors in the rat brain and liver after chronic treatment with various irre- versible and reversible monoamine oxidase (MAO) inhibitors. 2 Chronic treatment (7-14 days) with the irreversible MAO inhibitors, phenelzine (1-20 mg kg-', i.p.), isocarboxazid (10 mg kg-', i.p.), clorgyline (3 mg kg-', i.p.) and tranylcypromine (10mg kg-', i.p.) markedly decreased (21-71%) the density of 12 imidazoline-preferring receptors in the rat brain and liver. In contrast, chronic treatment (7 days) with the reversible MAO-A inhibitors, moclobemide (1 and 10 mg kg-', i.p.) or chlordimeform (10 mg kg-', i.p.) or with the reversible MAO-B inhibitor Ro 16-6491 (1 and 10 mg kg-', i.p.) did not alter the density of 12 imidazoline-preferring receptors in the rat brain and liver; except for the higher dose of Ro 16-6491 which only decreased the density of these putative receptors in the liver (38%). 3 In vitro, phenelzine, clorgyline, 3-phenylpropargylamine, tranylcypromine and chlordimeform dis- placed the binding of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors from two distinct binding sites.
    [Show full text]
  • Acrolein As a Novel Therapeutic Target for Motor and Sensory Deficits in Spinal Cord Injury
    [Downloaded free from http://www.nrronline.org on Wednesday, September 11, 2019, IP: 128.210.106.129] NEURAL REGENERATION RESEARCH April 2014,Volume 9,Issue 7 www.nrronline.org SPECIAL ISSUE Acrolein as a novel therapeutic target for motor and sensory deficits in spinal cord injury Jonghyuck Park1, 2, Breanne Muratori2, Riyi Shi1, 2 1 Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA 2 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA Abstract Corresponding author: In the hours to weeks following traumatic spinal cord injuries (SCI), biochemical processes are Riyi Shi, M.D., Ph.D., initiated that further damage the tissue within and surrounding the initial injury site: a process Department of Basic Medical Sciences, termed secondary injury. Acrolein, a highly reactive unsaturated aldehyde, has been shown to play College of Veterinary Medicine, Purdue a major role in the secondary injury by contributing significantly to both motor and sensory defi- University, West Lafayette, IN 47907, cits. In particular, efforts have been made to elucidate the mechanisms of acrolein-mediated dam- USA, [email protected]. age at the cellular level and the resulting paralysis and neuropathic pain. In this review, we will highlight the recent developments in the understanding of the mechanisms of acrolein in motor doi:10.4103/1673-5374.131564 and sensory dysfunction in animal models of SCI. We will also discuss the therapeutic benefits of http://www.nrronline.org/ using acrolein scavengers to attenuate acrolein-mediated neuronal damage following SCI. Accepted: 2014-04-08 Key Words: oxidative stress; spinal cord injury; 3-hydrxypropyl mercapturic acid; acrolein-lysine ad- duct; hydralazine Park J, Muratori B, Shi RY.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,784,177 B2 Cohn Et Al
    USOO6784177B2 (12) United States Patent (10) Patent No.: US 6,784,177 B2 Cohn et al. (45) Date of Patent: Aug. 31, 2004 (54) METHODS USING HYDRALAZINE Massie et al., The American Journal of Cardiology, COMPOUNDS AND SOSORBIDE 40:794-801 (1977). DINTRATE OR ISOSORBIDE Kaplan et al., Annals of Internal Medicine, 84:639-645 MONONTRATE (1976). Bauer et al., Circulation, 84(1):35-39 (1991). (75) Inventors: Jay N. Cohn, Minneapolis, MN (US); The SOLVD Investigators, The New England Journal of Medicine, 327(10):685–691 (1992). Peter Carson, Chevy Chase, MD (US) Ziesche et al., Circulation, 87(6):VI56-VI64 (1993). Rector et al., Circulation, 87(6):VI71-VI77 (1993). (73) Assignee: Nitro Med, Inc., Bedford, MA (US) Carson et al., Journal of Cardiac Failure, 5(3):178-187 (Sep. 10, 1999). (*) Notice: Subject to any disclaimer, the term of this Dries et al, The New England Journal of Medicine, patent is extended or adjusted under 35 340(8):609-616 (Feb. 25, 1999). U.S.C. 154(b) by 18 days. Freedman et al, Drugs, 54 (Supplement 3):41-50 (1997). Sherman et al., Cardiologia, 42(2):177-187 (1997). (21) Appl. No.: 10/210,113 Biegelson et al., Coronary Artery Disease, 10:241-256 (1999). (22) Filed: Aug. 2, 2002 Rudd et al, Am. J. Physiol., 277(46):H732–H739 (1999). (65) Prior Publication Data Hammerman et al, Am. J. Physiol., 277(46):H1579–1592 (1999). US 2004/0023967 A1 Feb. 5, 2004 LoScalzo et al., Transactions of the American and Climato logical ASS., 111:158-163 (2000).
    [Show full text]
  • Nialamide; SOCIETIES and LECTURES CORRECTION
    414 BRITISH MEDICAL JOURNAL 15 MAY 1971 care, and administration of health services. A. Clements, P. A. Connell, Patricia A. Crawford, G. A. Cupper, M. R. Dean, L. L. Dom- "It is, in short, medicine applied to a group SOCIETIES AND LECTURES bey, D. P. De Bono, J. P. Delamere, Gil- than to an individual patient." The lean P. Duncan, D. B. Dunger, C. E. G. Farqu- rather Br Med J: first published as 10.1136/bmj.2.5758.414 on 15 May 1971. Downloaded from statement adds that it is hoped that the pro- For attending lectures marked * a fee is charged or harson, Pamela C. Fenney, Daphne C. Fielding, a ticket is required. Applications should be made I. R. Fletcher, M. S. Fletcher, Po-Kai Fok, G. J. visional Faculty will be in a position to re- Frost, R. M. Galbraith, Elizabeth A. S. Galvin, first to the institution concerned. D. J. Giraldi, Jenifer I. Glover, B. A. Greenway, ceive applications from those wishing to be- Mary Griffin, J. F. Hamlyn, M. H. Hampton, come founder members later in the year. Monday, 17 May G. P. Harris, P. B. Harvey, A. C. Hillyard, Gillian M. M. Hodge, N. Holmes, Sheilagh M. Further announcements will be made. ABERDEEN UNIVERSITY.-At Medical Buildings, Hope, C. C. Hugh, Joanna E. Ide, Alison Ironside, Foresterhill, 5.30 p.m., dentj centennial lecture Keatley E. James, W. J. Jarrett, Celia A. Jenkins, by Sir Robert Bradlaw: Pigmentation. J. R. Jenner, P. D. Jones, C. L. Kennedy, N. D. Monoamine-oxidase Inhibitors INSTITUTE OF DERMATOLOGY.-4.30 p.m., Mr.
    [Show full text]