DOCSLIB.ORG

Effects of Acetorphan, an Enkephalinase Inhibitor, on Experimental and Acute Diarrhoea

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effects of Acetorphan, an Enkephalinase Inhibitor, on Experimental and Acute Diarrhoea Gut, 1992, 33, 753-758 753 Effects ofacetorphan, an enkephalinase inhibitor, on experimental and acute diarrhoea Ph Baumer, E Danquechin Dorval, J Bertrand, J M Vetel, J C Schwartz, J M Lecomte Abstract and reduce the discomfort. Their beneficial Acetorphan is an orally active inhibitor of effect, however, has become a matter of contro- enkephalinase (EC 3.4.24.11) with antidiar- versy in view of their limited efficacy and poten- rhoeal activity in rodents apparently through tial side effects. These drugs disrupt forward protection of endogenous enkephalins and a propulsive motility, increase capacitance of the purely antisecretory mechanism. Its antidiar- gut and delay passage of fluid through the rhoeal activity in man was assessed in an intestine allowing, in turn, more time for net experimental model of cathartic induced absorption of water and electrolytes to occur.68 secretory diarrhoea as well as in acute diar- The fact that their antidiarrhoeal activity is rhoea. of presumed infectious origin. In six always associated with an antimotility effect is healthy volunteers receiving castor oil and probably responsible for some of the major pretreated with acetorphan or placebo in a gastrointestinal side effects - that is, pooling of crossover controlled trial, the drug signific- fluid in the distended bowel lumen and enhance- antly decreased the number and weight of ment of bacterial colonisation.8"'3 This has led to stools passed during 24 hours. About 200 the idea that antidiarrhoeal drugs with a purely outpatients with severe acute diarrhoea (more mucosal antisecretory activity, should lead to a than five stools per day) were included in a therapeutic improvement.3 Two main strategies randomised double blind study of acetorphan were used to reach this aim: design weak a2- against placebo. The significant antidiarrhoeal adrenergic receptor blocks devoid of cardiovas- activity of acetorphan was established using a cular effects'45 and enkephalin like pentapep- variety of criteria: (i) the duration of both tides'"'8 but, so far, the resulting investigational diarrhoea and treatment were diminished; (ii) drugs have not gained therapeutic application. no acetorphan treated patient withdrew from Another strategy was recently suggested the study whereas five dropped out because of by the observations that inhibition of enkepha- worsening in the placebo group; (iii) the fre- linase (membrane metalloendopeptidase, EC quency ofsymptoms associated with diarrhoea 3.4.24.11) delays the inactivation of endogenous - for example, abdominal pain or distension, enkephalins in the brain which, in turn, results nausea and anorexia - remaining after two in a series of naloxone reversible biological weeks was nearly halved; (iv) using visual responses.'9 21 The peptidase is present all along analogue scales acetorphan treatment was the gastrointestinal tract2223 and its inhibition found more effective than placebo by both delays the inactivation of exogenous enkephalins investigators and patients. There was statistic- by the guinea pig ileum.2>26 Moreover, enkepha- ally no significant difference between acetor- linase inhibitors exert potent, naloxone revers- phan and placebo in respect of side effects, ible antidiarrhoeal activity in the rodent castor Laboratoire Bioprojet, particularly constipation, which often accom- oil induced model of diarrhoea.2728 Interestingly, Marnes la Coquette, panies the antidiarrhoeal activity of mu opioid this action was not associated with any detectable France this difference is attribut- antitransit effect,27 30 which clearly differentiates Ph Baumer receptor agonists J M Lecomte able to the lack of antipropulsive activity of this class of compounds from mu opiate receptor acetorphan in man. The efficacy and tolerance agonists.3'-36 Centre Hospitalier of acetorphan suggest that enkephalinase In the present study we have assessed the Universitaire Trousseau, Tours, France inhibition may represent a novel therapeutic antidiarrhoeal activity of the enkephalinase E Danquechin Dorval approach for the symptomatic management of inhibitor acetorphan in man in two randomised J Bertrand acute secretory diarrhoea without impairing placebo controlled double blind trials. The first trial on six healthy volunteers Centre Hospitalier intestinal transit. was a crossover Regional, Le Mans, receiving castor oil, a validated model of experi- France mental 'secretory' diarrhoea in man,'6 37 whereas J M Vetel It is generally admitted that acute infectious the second one was a parallel study on two groups Unite de Neurobiologie et diarrhoea is accompanied with an abnormality of ofabout 100 patients each attending their general Pharmacologie, Centre intestinal water and electrolyte transport. ' As a practitioners for severe acute diarrhoea of pre- Paul Broca de l'Institut with replacement of sumed infectious origin. National de la Sante et de consequence rehydration la Recherche Medicale, electrolytes are accepted as the most important Paris, France therapeutic measures. Antimicrobial agents are J C Schwartz also of value in diarrhoea caused by identified Methods Correspondence to: intestinal protozoa but are essentially ineffective Dr J C Schwartz, Unite de Neurobiologie et in the treatment of viral enteric infections which STUDY I: CASTOR OIL INDUCED DIARRHOEA Pharmacologie de l'Institut constitute most cases of acute diarrhoea.245 In National de la Sante et de la Recherche Medicale, Centre addition, mu opiate receptor agonists such as SUBJECTS Paul Broca, 2ter rue d'Alesia, opium derived preparations, diphenoxylate or Six healthy volunteers, three men, three women, 75014 Paris, France. are used to shorten the dura- aged 21 (3) years, with no reported digestive Accepted for publication loperamide widely 16 September 1991 tion of the disease, relieve a variety of symptoms abnormality, particularly no intestinal transit 754 Baumer, Danquechin Dorval, Bertrand, Vetel, Schwartz, Lecomte disorder, and not receiving any drug treatment, TREATMENT were selected. Their mean (SEM) body weights Identical capsules containing 100 mg either were 61-0 (3.7) kg (68 (4) kg for men, 54 (3) kg accetorphan or lactose (placebo) were supplied. for women). Written informed consent was Each patient was assigned a sequential study obtained and the study was approved by the local number and corresponding bottle containing 60 Ethical Committee. capsules. Treatment had been previously randomised using a random number table with groups of four. STUDY DESIGN Patients were given two capsules at the start of The study was a double blind, randomised, the study and were instructed to take one capsule placebo controlled crossover study ofthe preven- after each unformed bowel movement. Drug tion by acetorphan ofdiarrhoea elicited by a fixed administration was continued until recovery, dose of castor oil. The study comprised two defined as the disappearance of any unformed sessions, performed at one week intervals, stool, or for a maximum of 10 days. The remain- during which the subjects received placebo and ing capsules were returned to the investigators acetorphan capsules in a randomised order. and were counted to determine the actual Neither the subjects nor the clinicians were number of capsules ingested. No other new aware of the nature of treatment. treatment was allowed during the trial, except In the morning ofeach session, generally after for paracetamol. one spontaneous stool, each subject absorbed five capsules and, 45 minutes later, 30 g castor oil (French Pharmacopoeia). The time and weight STUDY DESIGN of each stool was then determined during the The patients were seen twice by clinicians not following 24 hours. informed of the nature oftreatments: for the first The capsules for the placebo session contained time at inclusion (visit 1) and 10-14 days later 200 mg lactose and were undiscernible from (visit 2). For each patient the clinicians had a case those containing acetorphan for which a dosage report form to complete at visits 1 and 2. It close to 10 mg/kg of body weight was selected. included a specific questionnaire with a report of The actual acetorphan dosage received by the clinical examinations. The clinicians remained subjects was 11 1 (4.2) mg/kg, a dosage eliciting blind all over the study. more than 50% inhibitions of plasma enkepha- Patients were requested to keep a diary in linase for at least six hours. which the following information was reported: All side effects were recorded during the 24 time, number and characters of bowel move- hour experimental period. ments, number of capsules taken, possible adverse affects, and their global evaluation of the treatment visual scales 0= STATISTICAL ANALYSIS using analogic (from The evaluation criteria were the cumulative no efficacy, to 100=excellent efficacy). Patients weights of stools, the total number of stools were asked to bring back the diary and remaining during the experimental 24 hour period and the capsules at visit 2 and both were checked by the delay between administration of the cathartic clinicians. and the first stool passage. Data were expressed The duration of diarrhoea was defined as the as means (SEM) and analysed by analysis of time from the first dose of the trial drug (visit 1) variance and Student's t test for matched series, to resolution of diarrhoea, that is the disappear- using the PCSM program (Deltasoft). Differ- ance of unformed stools. ences were considered significant at a 5% prob- The tolerance was assessed using the spon- level. taneously described
Load more

Recommended publications
  • Eluxadoline: a Treatment for IBS with Diarrhoea in Adults
    ■ NEW PRODUCT Eluxadoline: a treatment for IBS with diarrhoea in adults STEVE CHAPLIN Eluxadoline (Truberzi) KEY POINTS is an oral mixed opioid- receptor agonist/ ■ Eluxadoline is an opioid-receptor agonist/antagonist with low systemic absorption antagonist licensed for ■ It is licensed for the treatment of irritable bowel syndrome with diarrhoea in the treatment of irritable adults and is recommended by NICE as a second-line agent bowel syndrome with ■ The recommended dosage is 75–100mg orally twice daily diarrhoea in adults. ■ In clinical trials, response rates were 27%–31% with eluxadoline and 19.5% with placebo after 26 weeks’ treatment This article examines its ■ Common adverse effects include constipation, nausea and abdominal pain properties, efficacy in ■ Pancreatitis and sphincter of Oddi spasm were uncommon adverse events clinical trials and side- ■ Treatment with eluxadoline costs £88.20 per month. effects. he initial management of irritable locally within the gastrointestinal tract, Tbowel syndrome (IBS) entails dietary slowing gastrointestinal transit, reducing and lifestyle change and treatment with urgency and improving stool consistency; antispasmodic agents.1 For people with its abuse potential is low. IBS and diarrhoea, loperamide is the anti- Eluxadoline is licensed for the treat- motility agent of first choice, adjusting the ment of IBS with diarrhoea in adults. The dose to achieve optimum stool consist- recommended dosage is 100mg twice ency. If this is unsatisfactory, treatment daily (reduced to 75mg twice daily if with a low-dose tricyclic antidepressant poorly tolerated). Treatment should be should be considered, with an SSRI a initiated at the lower dose in older people further option if this is unsuccessful.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,692,728 B2 Weipert Et Al
    USOO6692728B2 (12) United States Patent (10) Patent No.: US 6,692,728 B2 Weipert et al. (45) Date of Patent: Feb. 17, 2004 (54) POLYESTERS BASED ON HYDROXY FATTY (52) U.S. Cl. ......................... 424/59; 424/497; 424/489; ACDS AND LOWER HYDROXY ALKYL 424/70.11; 424/78.37; 424/78.08; 514/785; ACDS AND USES THEREOF 560/171; 560/172; 560/176; 560/183; 525/400 (58) Field of Search .......................... 424/59, 497, 489, (75) Inventors: Paul David Weipert, High Point, NC 424/70.11, 78.37; 514/785; 560/172,176, (US); Bharat B. Desai, Spartanburg, 183; 525/400 SC (US) (73) Assignee: Ethox Chemicals LLC, Greenville, SC ") References Cited (US) U.S. PATENT DOCUMENTS ( c: ) Notice: Subject to any disclaimer, the term of this 5,502,116 A 3/1996 Noda ......................... 525/415 patent is extended or adjusted under 35 5,614,576 A * 3/1997 Rutherford et al. ......... 524/270 U.S.C. 154(b) by 0 days. 5,851,937 A * 12/1998 Wu et al. ................... 442/394 * cited by examiner (21) Appl. No.: 10/388,426 (22) Filed: Mar 17, 2003 Primary Examiner Sabiha Qazi 9 (74) Attorney, Agent, or Firm-Isaac A. Angres (65) Prior Publication Data (57) ABSTRACT US 2003/0175222 A1 Sep. 18, 2003 The present invention provides biodegradable polyesters Related U.S. Application Data based on lower hydroxy acids and hydroxy fatty acids. The resulting polyesters are useful as cosmetic vehicles for (62) Division of application No. 09/805,894, filed on Mar. 15, Sunscreens, skin lotions and by themselves are also useful as 2001, now Pat.
    [Show full text]
  • Adansonia Digitata L
    Veterinary World, EISSN: 2231-0916 RESEARCH ARTICLE Available at www.veterinaryworld.org/Vol.7/July-2014/10.pdf Open Access Antidiarrhoeal effect of the crude methanol extract of the dried fruit of Adansonia digitata L. (Malvaceae) Mohammed Musa Suleiman1111 , Mohammed Mamman , Ibrahim Hassan , Shamsu Garba , Mohammed Umaru Kawu21 and Patricia Ishaku Kobo 1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria; 2. Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria. Corresponding author: Mohammed Musa Suleiman, email:[email protected] MM: [email protected], IH: [email protected], SG: [email protected], MUK: [email protected], PIK: [email protected] Received:06-04-2014, Revised: 12-06-2014, Accepted: 14-06-2014, Published online: 19-07-2014 doi: 10.14202/vetworld.2014.495-500 How to cite this article: Suleiman MM, Mamman M, Hassan I, Garba S, Kawu MUand Kobo PI (2014) Antidiarrhoeal effect of the crude methanol extract of the dried fruit ofAdansonia digitata L. (Malvaceae), Veterinary World 7(7): 495-500. Abstract Aim: The study was designed to evaluate the antidiarrhoeal property of the methanol extract of the fruit of Adansonia digitata using laboratory animal models. Materials and Methods : The acute oral toxicity (LD50 ) of the extract was determined in mice, while the antidiarrhoeal effect of different doses of the extract was evaluated in both mice and rats. The effect of the extract at doses of 300, 700 and 1000 mg/kg were tested against intestinal transit time, magnesium sulphate-induced gastrointestinal motility test and castor oil- induced diarrhoea in mice.
    [Show full text]
  • FDA Warns About an Increased Risk of Serious Pancreatitis with Irritable Bowel Drug Viberzi (Eluxadoline) in Patients Without a Gallbladder
    FDA warns about an increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder Safety Announcement [03-15-2017] The U.S. Food and Drug Administration (FDA) is warning that Viberzi (eluxadoline), a medicine used to treat irritable bowel syndrome with diarrhea (IBS-D), should not be used in patients who do not have a gallbladder. An FDA review found these patients have an increased risk of developing serious pancreatitis that could result in hospitalization or death. Pancreatitis may be caused by spasm of a certain digestive system muscle in the small intestine. As a result, we are working with the Viberzi manufacturer, Allergan, to address these safety concerns. Patients should talk to your health care professional about how to control your symptoms of irritable bowel syndrome with diarrhea (IBS-D), particularly if you do not have a gallbladder. The gallbladder is an organ that stores bile, one of the body’s digestive juices that helps in the digestion of fat. Stop taking Viberzi right away and get emergency medical care if you develop new or worsening stomach-area or abdomen pain, or pain in the upper right side of your stomach-area or abdomen that may move to your back or shoulder. This pain may occur with nausea and vomiting. These may be symptoms of pancreatitis, an inflammation of the pancreas, an organ important in digestion; or spasm of the sphincter of Oddi, a muscular valve in the small intestine that controls the flow of digestive juices to the gut. Health care professionals should not prescribe Viberzi in patients who do not have a gallbladder and should consider alternative treatment options in these patients.
    [Show full text]
  • Glucose-Uptake Activity and Cytotoxicity of Diterpenes and Triterpenes Isolated from Lamiaceae Plant Species
    molecules Article Glucose-Uptake Activity and Cytotoxicity of Diterpenes and Triterpenes Isolated from Lamiaceae Plant Species Ninon G. E. R. Etsassala 1 , Kadidiatou O. Ndjoubi 2 , Thilly J. Mbira 2, Brendon Pearce 3 , Keenau Pearce 3, Emmanuel I. Iwuoha 4 , Ahmed A. Hussein 2 and Mongi Benjeddou 3,* 1 Department of Horticultural Sciences, Cape Peninsula University of Technology, Symphony Rd., Bellville 7535, South Africa; [email protected] 2 Chemistry Department, Cape Peninsula University of Technology, Symphony Rd., Bellville 7535, South Africa; [email protected] (K.O.N.); [email protected] (T.J.M.); [email protected] (A.A.H.) 3 Precision Medicine Laboratory, Department of Biotechnology, 2nd Floor, Life Science Building, University of the Western Cape, Cape Town 7530, South Africa; brendon.biff@gmail.com (B.P.); [email protected] (K.P.) 4 Chemistry Department, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa; [email protected] * Correspondence: [email protected]; Tel.: +27-21-959-2080; Fax: +27-21-959-3505 Academic Editors: Patrícia Rijo, Vera Isca and Daniele Passarella Received: 17 July 2020; Accepted: 14 August 2020; Published: 10 September 2020 Abstract: The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rates of morbidity and mortality around the world in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristics of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species: namely, Salvia africana-lutea, Leonotis ocymifolia, and Plectranthus madagascariensis, for their glucose-uptake ability.
    [Show full text]
  • In Vivo Evaluation of Antidiarrhoeal Activity of the Leaves of Azima Tetracantha Linn
    Vol.5(8), pp. 140-144, December, 2013 DOI: 10.5897/IJNAM2013.0152 International Journal of Nutrition and ISSN 2141-2340 ©2013 Academic Journals http://www.academicjournals.org/IJNAM Metabolism Full Length Research Paper In vivo evaluation of antidiarrhoeal activity of the leaves of Azima tetracantha Linn V. Hazeena Begum*, M. Dhanalakshmi and P. Muthukumaran Department of Siddha Medicine, Faculty of Science, Tamil University, Vakaiyur, Thanjavur 613 010, Tamilnadu, India. Accepted 3 October, 2013 The aqueous crude extract of the leaves of Azima tetracantha was studied for its phytochemical constituents and antidiarrhoeal activity using castor oil-induced diarrhoea and castor oil-induced enteropooling in rats. The phytochemical studies of the aqueous extract revealed the presence of alkaloids, flavonoids, tannins and saponins. The extract showed significant (p < 0.001) protection against castor oil-induced diarrhoea and castor oil-induced enteropooling at (100 mg/kg). The presence of some of the phytochemicals in the root extract may be responsible for the observed effects, and also the basis for its use in traditional medicine as antidiarrhoeal drug. Key words: Azima tetracantha, enteropooling, anti-diarrhoeal. INTRODUCTION Diarrhoea is characterized by increased frequency of powerful diuretic given in rheumatism, dropsy, dyspepsia bowel movement, wet stool and abdominal pain and chronic diarrhoea and as a stimulant tonic after (Ezekwesili et al., 2004). It is a leading cause of confinement (Nadkarni, 1976). A. tetracantha as efficient malnutrition and death among children in the developing acute phase anti-inflammatory drug is traditionally used countries of the world today (Victoria et al., 2000). Many by Indian medical practitioners (Ismail et al., 1997).
    [Show full text]
  • Information to Users
    The direct and modulatory antinociceptive actions of endogenous and exogenous opioid delta agonists Item Type text; Dissertation-Reproduction (electronic) Authors Vanderah, Todd William. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 04/10/2021 00:14:57 Link to Item http://hdl.handle.net/10150/187190 INFORMATION TO USERS This ~uscript }las been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely. event that the author did not send UMI a complete mannscript and there are missing pages, these will be noted Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginnjng at the upper left-hand comer and contimJing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy.
    [Show full text]
  • Supplementary Information
    Supplementary Information Network-based Drug Repurposing for Novel Coronavirus 2019-nCoV Yadi Zhou1,#, Yuan Hou1,#, Jiayu Shen1, Yin Huang1, William Martin1, Feixiong Cheng1-3,* 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA 2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA 3Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA #Equal contribution *Correspondence to: Feixiong Cheng, PhD Lerner Research Institute Cleveland Clinic Tel: +1-216-444-7654; Fax: +1-216-636-0009 Email: [email protected] Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. Supplementary Table S2. Protein sequence identities across 5 protein regions in 15 coronaviruses. Supplementary Table S3. HCoV-associated host proteins with references. Supplementary Table S4. Repurposable drugs predicted by network-based approaches. Supplementary Table S5. Network proximity results for 2,938 drugs against pan-human coronavirus (CoV) and individual CoVs. Supplementary Table S6. Network-predicted drug combinations for all the drug pairs from the top 16 high-confidence repurposable drugs. 1 Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. GenBank ID Coronavirus Identity % Host Location discovered MN908947 2019-nCoV[Wuhan-Hu-1] 100 Human China MN938384 2019-nCoV[HKU-SZ-002a] 99.99 Human China MN975262
    [Show full text]
  • Enkephalin Degradation in Serum of Patients with Inflammatory Bowel Diseases
    Pharmacological Reports 71 (2019) 42–47 Contents lists available at ScienceDirect Pharmacological Reports journal homepage: www.elsevier.com/locate/pharep Original article Enkephalin degradation in serum of patients with inflammatory bowel diseases a, a b Beata Wilenska *, Dagmara Tymecka , Marcin Włodarczyk , b c Aleksandra Sobolewska-Włodarczyk , Maria Wisniewska-Jarosinska , d e b a,d, Jolanta Dyniewicz , Árpád Somogyi , Jakub Fichna , Aleksandra Misicka * a Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warszawa, Poland b Department of Biochemistry, Medical University of Lodz, Łódz, Poland c Department of Gastroenterology, Medical University of Lodz, Łódz, Poland d Department of Neuropeptides, Mossakowski Medical Research Centre Polish Academy of Science, Warszawa, Poland e Campus Chemical Instrumentation Centre (CCIC), The Ohio State University, Columbus, OH, USA A R T I C L E I N F O A B S T R A C T Article history: Background: Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal Received 18 April 2018 disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the Received in revised form 10 June 2018 endogenous opioid system has been proposed. Consequently, due to the fact that endogenous Accepted 1 August 2018 enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum Available online 2 August 2018 enkephalin (Met- and Leu-enkephalin) in patients with IBD. Methods: Enkephalin degradation in serum of patients with IBD was characterized using mass Keywords: spectrometry methods. Calculated half-life (T1/2) of enkephalins were compared and correlated with the Inflammatory bowel diseases disease type and gender of the patients.
    [Show full text]
  • Title Page Behavioral Effects and CNS Levels of the Broadly
    JPET Fast Forward. Published on March 20, 2012 as DOI: 10.1124/jpet.112.193227 JPET FastThis article Forward. has not beenPublished copyedited on and Marchformatted. 20, The 2012 final version as DOI:10.1124/jpet.112.193227 may differ from this version. JPET #193227 Title Page Behavioral effects and CNS levels of the broadly available κ-agonist hallucinogen salvinorin A are affected by p-glycoprotein modulation in vivo Downloaded from jpet.aspetjournals.org Eduardo R. Butelman, Michael Caspers, Kimberly M. Lovell, Mary Jeanne Kreek, Thomas E. Prisinzano at ASPET Journals on September 28, 2021 The Rockefeller University, New York, NY 10024 (ERB, MJK), and Department of Medicinal Chemistry, University of Kansas School of Pharmacy, Lawrence, KS 66045 (MC, KML, TEP) 1 Copyright 2012 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on March 20, 2012 as DOI: 10.1124/jpet.112.193227 This article has not been copyedited and formatted. The final version may differ from this version. JPET #193227 Running Title Page a) Running Title: p-glycoprotein and salvinorin A effects b) Corresponding author: E.R. Butelman, The Rockefeller University (Box 171), 1230 York Ave, New York NY 10065. Downloaded from Phone: (212)327-8247 FAX: (212)327-8574 e-mail: [email protected] jpet.aspetjournals.org c) Number of text pages: 25 Number of Tables: 1 Number of Figure: 6 Number of References: 38 Number of words in the Abstract: 250 at ASPET Journals on September 28, 2021 Number of words in the Introduction: 423 Number of words in the Discussion: 668 d) Nonstandard abbreviations used in the paper: BBB: blood-brain barrier; p-gp: p-glycoprotein; PT: pre-treatment e) Recommended section assignment: Behavioral pharmacology 2 JPET Fast Forward.
    [Show full text]
  • Redalyc.Changes, Functional Disorders, and Diseases in the Gastrointestinal Tract of Elderly
    Nutrición Hospitalaria ISSN: 0212-1611 info@nutriciónhospitalaria.com Grupo Aula Médica España Grassi, M.; Petraccia, L.; Mennuni, G.; Fontana, M.; Scarno, A.; Sabetta, S.; Fraioli, A. Changes, functional disorders, and diseases in the gastrointestinal tract of elderly Nutrición Hospitalaria, vol. 26, núm. 4, julio-agosto, 2011, pp. 659-668 Grupo Aula Médica Madrid, España Available in: http://www.redalyc.org/articulo.oa?id=309226773001 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative Nutr Hosp. 2011;26(4):659-668 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Revisión Changes, functional disorders, and diseases in the gastrointestinal tract of elderly M. Grassi1, L. Petraccia1, G. Mennuni1, M. Fontana2, A. Scarno1, S. Sabetta1 and A. Fraioli1 1Deparment Internal Medicine and Medical Disciplines. Unit of Internal Medicine E, Medical Therapy and Thermal Medicine - School of Specialization in Thermal Medicine. 2Department of Biochemical Sciences. Sapienza University of Rome. Rome. Italy. Abstract CAMBIOS, DOLENCIAS FUNCIONALES Y ENFERMEDADES EN EL SISTEMA This article describes changes in the basic digestive GASTROINTESTINAL EN PERSONAS MAYORES functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and Resumen altered swallowing of food. Reductions in esophageal Este artículo describe los cambios en las funciones peristalsis and lower esophageal sphincter (LES) pres- digestivas básicas (motilidad, secreción, digestión intralu- sures are also more common in the aged and may cause minal, absorción) que ocurren en el envejecimiento.
    [Show full text]
  • PRODUCT INFORMATION Spinorphin Item No
    PRODUCT INFORMATION Spinorphin Item No. 29914 NH CAS Registry No.: 137201-62-8 Formal Name: L-leucyl-L-valyl-L-valyl-L-tyrosyl-L- O H O N prolyl-L-tryptophyl-L-threonine N OH O N H Synonyms: Leu-Val-Val-Tyr-Pro-Trp-Thr, O OH H LVVYPWT O O N MF: C45H64N8O10 N N O FW: 877.0 H H NH2 Purity: ≥95% UV/Vis.: λmax: 222 nm Supplied as: A crystalline solid Storage: -20°C OH Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Spinorphin is supplied as a crystalline solid. A stock solution may be made by dissolving the spinorphin in the solvent of choice, which should be purged with an inert gas. Spinorphin is soluble in organic solvents such as DMSO and dimethyl formamide. The solubility of spinorphin in these solvents is approximately 30 mg/ml. Description Spinorphin is a heptapeptide inhibitor of the enkephalin-degrading enzymes aminopeptidase, dipeptidyl aminopeptidase, angiotensin-converting enzyme (ACE), and enkephalinase (IC50s = 3.3, 1.4, 2.4, and 10 µg/ml, respectively, for monkey brain enzymes).1 It is selective for these enzymes over human serum aminopeptidase A (IC50 = >100 µg/ml), as well as porcine kidney aminopeptidase B, aminopeptidase M, dipeptidyl peptidase 1 (DPP-1), DPP-2, DPP-3, and DPP-4 (IC50s = >55 µg/ml for all). Spinorphin inhibits chemotaxis, production of reactive oxygen species (ROS), and exocytosis of glucuronidase and collagenase in polymorphonuclear neutrophils (PMNs). It potentiates enkephalin-induced action potentials in rat hippocampal slices.
    [Show full text]