DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2008/0113037 A1 Green Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2008/0113037 A1 Green Et Al US 2008011.3037A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0113037 A1 Green et al. (43) Pub. Date: May 15, 2008 (54) TOPICAL COMPOSITIONS COMPRISING Publication Classification POLYHYDROXY ACIDS AND/OR LACTONES (51) Int. Cl. FOR IMPROVED CUTANEOUSEFFECTS OF A633/40 (2006.01) OXDATIVE THERAPEUTC DRUGS A6II 3/34 (2006.01) A63L/385 (2006.01) A633/04 (2006.01) (76) Inventors: Barbara A. Green, Edison, NJ A6II 47/12 (2006.01) (US); David J. Milora, Blue Bell, A6IP 700 (2006.01) PA (US) A6II 35/04 (2006.01) A633/22 (2006.01) Correspondence Address: A633/32 (2006.01) GOODWIN PROCTER LLP (52) U.S. Cl. ......... 424/616; 424/640; 424/660; 424/667; 901 NEW YORKAVENUE, N.W. 424/703; 424/725.1: 514/18: 514/356; 514/440; WASHINGTON, DC 20001 514/460, 514/714: 514/785 (57) ABSTRACT (21) Appl. No.: 11/682,039 Embodiments relate generally to topical compositions useful for treating or preventing a variety of cosmetic conditions and dermatological disorders, where the composition comprises an oxidative pharmaceutical drug and an antioxidant polyhy (22) Filed: Mar. 5, 2007 droxy acid or polyhydroxylactone. The polyhydroxy acid or polyhydroxy lactone improves the cutaneous effects of the Related U.S. Application Data drug. The embodiments further relate to the treatment of a variety of cosmetic conditions and dermatological disorders (60) Provisional application No. 60/865.244, filed on Nov. comprising administering to a subject an effective amount of 10, 2006. the composition and to methods of making the compositions. US 2008/O 113037 A1 May 15, 2008 TOPCAL COMPOSITIONS COMPRISING is a method of making a composition for topical administra POLYHYDROXY ACDS AND/OR LACTONES tion that can be useful for treating a variety of cosmetic FOR IMPROVED CUTANEOUSEFFECTS OF conditions and dermatological disorders, where the compo OXDATIVE THERAPEUTIC DRUGS sition comprises an oxidative pharmaceutical drug and a polyhydroxy acid or polyhydroxy lactone. CROSS-REFERENCE TO RELATED APPLICATION DETAILED DESCRIPTION OF THE PREFERRED 0001. This application claims benefit of U.S. Provisional EMBODIMENTS Application No. 60/865,244, filed on Nov. 10, 2006, which is 0008. The terminology used herein is for the purpose of hereby incorporated by reference in its entirety. describing particular embodiments only, and is not intended to limit the scope of the present invention. As used throughout FIELD OF THE INVENTION this disclosure, the singular forms “a,” “an and “the include 0002 Embodiments relate generally to topical composi plural references unless the context clearly dictates other tions useful for treating or preventing a variety of cosmetic wise. conditions and dermatological disorders, where the compo 0009. Oxidative pharmaceutical drugs can be chemical sition comprises an oxidative pharmaceutical drug and a compounds that contain at least one oxidative functional polyhydroxy acid or polyhydroxy lactone. The polyhydroxy group or that function as oxidative Substances when topically acid or polyhydroxy lactone improves the cutaneous effects applied to the cutaneous tissue. Such as peroxide, peracid, of the drug. The embodiments further relate to the treatment Superoxide and the like. Examples of Such drugs are benzoyl of variety of cosmetic conditions and dermatological disor peroxide, carbamide peroxide, coal tar, glutathione, hydro ders comprising administering to a Subject an effective gen peroxide, iodine, juniper tar, lipoic acid, NAD", amount of the composition and to methods of making the NADP", nitrogen oxide, oxygen, pine tar, potassium per compositions. manganate, povidone-iodine, perbenzoic acid, Sulfur, Sulfur dioxide, Sodium borate, Sodium perborate, shale tar, DESCRIPTION OF RELATED ART ubiquinone and wood tar. 0010 When an oxidative pharmaceutical drug is adminis 0003 Oxidative pharmaceutical drugs can be chemical tered to cutaneous tissues including the skin for topical treat compounds that contain at least one oxidative functional ment, adverse reactions occur. The adverse reactions to the group or that function as oxidative substances when topically skin include (a) dryness, (b) irritation, (c) erythema, (d) dam applied to the skin, such as peroxide, peracid, Superoxide and age and (e) other miscellaneous side effects. These adverse the like. Examples of such drugs are benzoyl peroxide, hydro reactions are not required for or are unrelated to the therapeu gen peroxide and perbenzoic acid. tic effects of the drug. The present inventors have discovered 0004. When an oxidative pharmaceutical drug is adminis that when a polyhydroxy acid or polyhydroxy lactone is tered to cutaneous tissues including the skin for topical treat incorporated into a composition comprising the oxidative ment of dermatological disorders, the adverse reactions to the pharmaceutical drug, the adverse reactions to the skin by the skin include (a) dryness, (b) irritation, (c) erythema, (d) dam drug are eliminated or minimized, and therapeutic efficacy is age and (e) other miscellaneous side effects. Such adverse maintained or enhanced. reactions and damages to the skin are not required for or are 0011. As an illustration, when a composition containing unrelated to the therapeutic effects of the drug. oxidative benzoyl peroxide is administered for topical treat 0005 U.S. Pat. No. 6,036,963 discloses the use of glu ment of acne, the skin becomes dry, erythematous and irri conolactone or glucarolactone in cosmetic skin care compo tated. Many subjects discontinue the use of Such composi sitions as an anti-irritant. The gluconolactone or glucarolac tions because of the adverse skin reactions. When a tone are said to alleviate or control any skin irritation that may composition comprising gluconolactone and oxidative ben be caused by glycolic acid. Zoyl peroxide is administered topically, however, there is less, or even no irritation, and the acne lesions are improved. SUMMARY OF INVENTION 0012 Polyhydroxy acids and polyhydroxy lactones pref 0006. It is desirable to minimize or eliminate the adverse erably are (a) modulators for skin keratinization, (b) antioxi reactions and damages to the skin caused by oxidative phar dant compounds, (c) preventive or counter-irritants, (d) mois maceutical drugs. These adverse reactions are not required turizers, (e) skin barrier strengtheners, (f) restorers when for or are unrelated to the therapeutic effects of the drug. The topically administered to cutaneous tissues; and (g) anti-ag present inventors have discovered that when a polyhydroxy ing compounds by increasing dermal biosynthesis. Polyhy acid or polyhydroxy lactone is incorporated into a composi droxy acids and polyhydroxy lactones typically are organic tion comprising the oxidative pharmaceutical drug, the carboxylic compounds having at least two hydroxyl groups in adverse reactions to the skin by the drugs are eliminated or the molecules and with preferred molecular weight of minimized. between about 100 and about 300. These polyhydroxy acids 0007. One embodiment of this invention is a composition and polyhydroxylactones include gluconic acid, gluconolac for topical administration comprising an oxidative pharma tone, ribonic acid, ribonolactone, galactonic acid, galactono ceutical drug and a polyhydroxy acid or polyhydroxylactone. lactone, glucoheptonic acid, glucoheptonolactone, glucu Another embodiment of this invention is a method of topical ronic acid, glucuronolactone, galacturonic acid, cutaneous treatment of a variety of cosmetic conditions and galacturonolactone, glucaric acid, glucarolactone, galactaric dermatological disorders comprising administering to a Sub acid and galactarolactone. ject an effective amount of a composition comprising an 0013 The polyhydroxyacids and polyhydroxylactones of oxidative pharmaceutical drug and a polyhydroxy acid or the present embodiments can be divided into the following polyhydroxy lactone. Another embodiment of this invention three groups. US 2008/O 113037 A1 May 15, 2008 0014 (A) Aldonic Acids and Aldonolactones idoheptaric acid and idoheptarolactone, galactoheptaric acid 0015. When a common carbohydrate, also called aldose, is and galactoheptarolactone, taloheptaric acid and taloheptaro oxidized at the carbon one position from an aldehyde to a lactone). carboxyl group, the product is called aldonic acid. For 0020 (C) Alduronic Acids and Alduronolactones. example, when glucose is oxidized at the carbon one position, 0021 Alduronic acid is typically obtained from a carbo the product is gluconic acid. The aldonic acid usually has hydrate, aldose, by oxidation of the terminal carbon to car multiple hydroxyl groups. The generic structure can be boxyl group, and the carbon one position remains as aldehyde shown as follows: group, Such as glucuronic acid from glucose. Similar to aldonic acid and aldaric acid, alduronic acid also has multiple R(CHOH),CHOHCOOH hydroxyl groups attached to the carbon chain between two where R is usually Horan alkyl group and n is an integer from functional groups, one aldehyde and one carboxyl groups in 1-9. The aldonic acids can exist as stereoisomers as D. L. and this case. Many alduronic acids exist as intramolecular lac DL or R,S and RS forms. Many aldonic acids form intramo tones, alduronolactones. Such as glucuronolactone from glu lecular lactones, aldonolactones, by removing one mole of curonic acid. The generic structure can be shown as follows: water between the carboxyl group and one hydroxyl group. HOOC(CHOH),CHOHCHO 0016. The following are representative aldonic
Load more

Recommended publications
  • Transdermal Drug Delivery Device Including An
    (19) TZZ_ZZ¥¥_T (11) EP 1 807 033 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61F 13/02 (2006.01) A61L 15/16 (2006.01) 20.07.2016 Bulletin 2016/29 (86) International application number: (21) Application number: 05815555.7 PCT/US2005/035806 (22) Date of filing: 07.10.2005 (87) International publication number: WO 2006/044206 (27.04.2006 Gazette 2006/17) (54) TRANSDERMAL DRUG DELIVERY DEVICE INCLUDING AN OCCLUSIVE BACKING VORRICHTUNG ZUR TRANSDERMALEN VERABREICHUNG VON ARZNEIMITTELN EINSCHLIESSLICH EINER VERSTOPFUNGSSICHERUNG DISPOSITIF D’ADMINISTRATION TRANSDERMIQUE DE MEDICAMENTS AVEC COUCHE SUPPORT OCCLUSIVE (84) Designated Contracting States: • MANTELLE, Juan AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Miami, FL 33186 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • NGUYEN, Viet SK TR Miami, FL 33176 (US) (30) Priority: 08.10.2004 US 616861 P (74) Representative: Awapatent AB P.O. Box 5117 (43) Date of publication of application: 200 71 Malmö (SE) 18.07.2007 Bulletin 2007/29 (56) References cited: (73) Proprietor: NOVEN PHARMACEUTICALS, INC. WO-A-02/36103 WO-A-97/23205 Miami, FL 33186 (US) WO-A-2005/046600 WO-A-2006/028863 US-A- 4 994 278 US-A- 4 994 278 (72) Inventors: US-A- 5 246 705 US-A- 5 474 783 • KANIOS, David US-A- 5 474 783 US-A1- 2001 051 180 Miami, FL 33196 (US) US-A1- 2002 128 345 US-A1- 2006 034 905 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • (12) United States Patent (10) Patent N0.: US 7,723,065 B2 Trewhella Et A]
    US007723065B2 (12) United States Patent (10) Patent N0.: US 7,723,065 B2 Trewhella et a]. (45) Date of Patent: May 25, 2010 (54) CONDITIONS FOR REACTIONS MEDIATED Kumar A, Ner DH, Dike SY, A New Chemoenzymatic Enantioselec BY YEAST tive Synthesis of R-(—)-Tomoxetine, R- and S-Fluoxetine, Tetrahe dron Letters, 1991, 32(16): 1901-1904.* (75) Inventors: Maurice Arthur TreWhella, Hoppers Liu X, Zhu T-S, Sun P-D, Xu J-H, Asymmetric Reduction of Aro Crossing (AU); Nick Athanasiou, matic Ketones by the Baker’s Yeast in Organic Solvent Systems, Yarraville (AU); Andrew John Synthetic Communications, 2001, 31(10): 1521-1526.* Smallridge, Hampton East (AU) Chem 231 Lecture No. 10 Sp 1999* Ohta et al. “Asymmeteric Reduction of Nitro Ole?ns by Fermment (73) Assignee: Victoria University, Victoria (AU) ing Baker’sYeast.” J. Org. Chem. vol. 54, pp. 1802-1804. 1989* ( * ) Notice: Subject to any disclaimer, the term of this KaWai et al. “Asymmeteric Reduction of nitroalkenes With baker’s patent is extended or adjusted under 35 yeast.” Tetrahedron: Asymmetry. vol. 12, pp. 309-318. 2001.* U.S.C. 154(b) by 933 days. Y. Gao and K. B. Sharpless-“Asymmetric Synthesis of Both Enantionmers of Tomoxentine and Fluoxentine. Selective Reduction of 2, 3-Epoxycinnamyl Alcohol With Red-A1”, J. Org. Chem. 1988, (21) Appl.No.: 10/814,891 53, 4081-4084. © 1988 American Chemical Society. (22) Filed: Mar. 31, 2004 Badan S. Deol et al., Asymmetric Reduction of Carbonyl Compounds byYeast. II; Aust. J. Chem., 1976, 29, 2459-67, 9 pages. (65) Prior Publication Data * cited by examiner US 2005/0084943 A1 Apr.
    [Show full text]
  • Treatment for Calcium Channel Blocker Poisoning: a Systematic Review
    Clinical Toxicology (2014), 52, 926–944 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2014.965827 REVIEW ARTICLE Treatment for calcium channel blocker poisoning: A systematic review M. ST-ONGE , 1,2,3 P.-A. DUB É , 4,5,6 S. GOSSELIN ,7,8,9 C. GUIMONT , 10 J. GODWIN , 1,3 P. M. ARCHAMBAULT , 11,12,13,14 J.-M. CHAUNY , 15,16 A. J. FRENETTE , 15,17 M. DARVEAU , 18 N. LE SAGE , 10,14 J. POITRAS , 11,12 J. PROVENCHER , 19 D. N. JUURLINK , 1,20,21 and R. BLAIS 7 1 Ontario and Manitoba Poison Centre, Toronto, ON, Canada 2 Institute of Medical Science, University of Toronto, Toronto, ON, Canada 3 Department of Clinical Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada 4 Direction of Environmental Health and Toxicology, Institut national de sant é publique du Qu é bec, Qu é bec, QC, Canada 5 Centre Hospitalier Universitaire de Qu é bec, Qu é bec, QC, Canada 6 Faculty of Pharmacy, Université Laval, Qu é bec, QC, Canada 7 Centre antipoison du Qu é bec, Qu é bec, QC, Canada 8 Department of Medicine, McGill University, Montr é al, QC, Canada 9 Toxicology Consulting Service, McGill University Health Centre, Montr é al, QC, Canada 10 Centre Hospitalier Universitaire de Qu é bec, Qu é bec, QC, Canada 11 Centre de sant é et services sociaux Alphonse-Desjardins (CHAU de Lévis), L é vis, QC, Canada 12 Department of Family Medicine and Emergency Medicine, Universit é Laval, Québec, QC, Canada 13 Division de soins intensifs, Universit é Laval, Qu é bec, QC, Canada 14 Populations
    [Show full text]
  • Role of Selective Α and Β Adrenergic Receptor Mechanisms in Rat Jejunal Longitudinal Muscle Contractility
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by RERO DOC Digital Library J Gastrointest Surg (2008) 12:1087–1093 DOI 10.1007/s11605-007-0327-4 Role of Selective α and β Adrenergic Receptor Mechanisms in Rat Jejunal Longitudinal Muscle Contractility Roland Seiler & Andreas Rickenbacher & Sidney Shaw & Simon Haefliger & Bruno M. Balsiger Received: 29 August 2007 /Accepted: 5 September 2007 /Published online: 19 September 2007 # 2007 The Society for Surgery of the Alimentary Tract Abstract Gut motility is modulated by adrenergic mechanisms. The aim of our study was to examine mechanisms of selective adrenergic receptors in rat jejunum. Spontaneous contractile activity of longitudinal muscle strips from rat jejunum was measured in 5-ml tissue chambers. Dose–responses (six doses, 10−7–3×10−5M) to norepinephrine (NE, nonspecific), phenylephrine (PH, α1), clonidine (C, α2), prenalterol (PR, β1), ritodrine (RI, β2), and ZD7714 (ZD, β3) were evaluated with and without tetrodotoxin (TTX, nerve blocker). NE(3 × 10−5M) inhibited 74 ± 5% (mean ± SEM) of spontaneous activity. This was the maximum effect. The same dose of RI(β2), PH(α1), or ZD(β3) resulted in an inhibition of only 56 ± 5, 43 ± 4, 33 ± 6, respectively. The calculated concentration to induce 50% inhibition (EC50) of ZD(β3) was similar to NE, whereas higher concentrations of PH(α1) or RI(β2) were required. C(α2) and PR(β1) had no effect. TTX changed exclusively the EC50 of RI from 4.4 ± 0.2 to 2.7 ± 0.8% (p < 0.04). Contractility was inhibited by NE (nonspecific).
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • I (Acts Whose Publication Is Obligatory) COMMISSION
    13.4.2002 EN Official Journal of the European Communities L 97/1 I (Acts whose publication is obligatory) COMMISSION REGULATION (EC) No 578/2002 of 20 March 2002 amending Annex I to Council Regulation (EEC) No 2658/87 on the tariff and statistical nomenclature and on the Common Customs Tariff THE COMMISSION OF THE EUROPEAN COMMUNITIES, Nomenclature in order to take into account the new scope of that heading. Having regard to the Treaty establishing the European Commu- nity, (4) Since more than 100 substances of Annex 3 to the Com- bined Nomenclature, currently classified elsewhere than within heading 2937, are transferred to heading 2937, it is appropriate to replace the said Annex with a new Annex. Having regard to Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Com- mon Customs Tariff (1), as last amended by Regulation (EC) No 2433/2001 (2), and in particular Article 9 thereof, (5) Annex I to Council regulation (EEC) No 2658/87 should therefore be amended accordingly. Whereas: (6) This measure does not involve any adjustment of duty rates. Furthermore, it does not involve either the deletion of sub- stances or addition of new substances to Annex 3 to the (1) Regulation (EEC) No 2658/87 established a goods nomen- Combined Nomenclature. clature, hereinafter called the ‘Combined Nomenclature’, to meet, at one and the same time, the requirements of the Common Customs Tariff, the external trade statistics of the Community and other Community policies concerning the (7) The measures provided for in this Regulation are in accor- importation or exportation of goods.
    [Show full text]
  • Beta-2 Adrenergic Effects on the Sympathetic Nervous System
    BETA-2 ADRENERGIC EFFECTS ON THE SYMPATHETIC NERVOUS SYSTEM. Beta-2 Adrenerge Effecten op het Sympathische Zenuwstelsel PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof. Dr. A.H.G. Rinnooy Kan en volgens besluit van het college van dekanen. De openbare verdediging zal plaatsvinden op woensdag 3 mei 1989 om 13.45 uur door Hieronymus Henricus Vincent geboren te Schiedam. 1 PROMOTIE-COMMISSIE Promotor: Prof. Dr. M. A.. D. H. Schalekamp Overige leden: Prof. Dr. W.H. Birkenhäger Prof. Dr. P.R. Saxena Dr. Th.A. Thien 2 CONTENTS Chapter 1: Introduetion .••.•...••...•.....•...•......• 5 Chapter 2: Elevated plasma noradrenaline in response to beta adrenoceptor stimulation in man ....•...•........ l3 Chapter 3: Effects of selective and non-selective beta agonists on plasma potassium and norepinephrine ...... l8 Chapter 4: Stress levels of adrenaline amplify the blood pressure response to sympathetic stimulation ... 26 Chapter 5: Is beta-l antagonism essential to the antihypertensive action of betablockers? ........... 32 Chapter 6: Beta-2 agonists increase plasma renin through beta-l adrenoceptor activatien by transmitter noradrenaline. Evidence for functional presynaptic beta recepters in the kidney ..•.••....•...••....• , ........ 3 8 Chapter 7: General discussion ........................ 52 Chapter 8: Samenvatting ..•.......•........••......... 60 Curriculum vitae .••.•.•....•..•.•.•.•..•........•...• 68 Dankwoord .......•..•....•..•....•...•................ 6 9 3 4 Chapter 1 INTRODUeTION The origin of the studies, described in this thesis, dates back to 1979. In that year my colleague, R.P. Verhoeven, studied the responsiveness of hyperthyroid patients to beta adrenoceptor activation [1]. In his experiments he made the serendipitous observation that the plasma levels of the sympathetic transmitter, noradrenaline, increased during infusion of the beta adrenoceptor agonist isoprenaline.
    [Show full text]
  • II the Thermodynamics of Efficacy and Ligand Proton Transfer
    Towards a Thermodynamic Definition of Efficacy in Partial Agonism: II The Thermodynamics of Efficacy and Ligand Proton Transfer in a G Protein-coupled Receptor of the Rhodopsin Class Kenneth J. Broadley, Shane C. Sykes, Robin H. Davies To cite this version: Kenneth J. Broadley, Shane C. Sykes, Robin H. Davies. Towards a Thermodynamic Definition of Efficacy in Partial Agonism: II The Thermodynamics of Efficacy and Ligand Proton Transferina G Protein-coupled Receptor of the Rhodopsin Class. Biochemical Pharmacology, Elsevier, 2010, 80 (10), pp.1537. 10.1016/j.bcp.2010.07.044. hal-00626230 HAL Id: hal-00626230 https://hal.archives-ouvertes.fr/hal-00626230 Submitted on 24 Sep 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Accepted Manuscript Title: Towards a Thermodynamic Definition of Efficacy in Partial Agonism: II The Thermodynamics of Efficacy and Ligand Proton Transfer in a G Protein-coupled Receptor of the Rhodopsin Class Authors: Kenneth J. Broadley, Shane C. Sykes, Robin H. Davies PII: S0006-2952(10)00583-6 DOI: doi:10.1016/j.bcp.2010.07.044 Reference: BCP 10678 To appear in: BCP Received date: 28-6-2010 Accepted date: 21-7-2010 Please cite this article as: Broadley KJ, Sykes SC, Davies RH, Towards a Thermodynamic Definition of Efficacy in Partial Agonism: II The Thermodynamics of Efficacy and Ligand Proton Transfer in a G Protein-coupled Receptor of the Rhodopsin Class, Biochemical Pharmacology (2010), doi:10.1016/j.bcp.2010.07.044 This is a PDF file of an unedited manuscript that has been accepted for publication.
    [Show full text]
  • Sympathetic NS
    Pharmacology of the Autonomic Nervous System Indented = similar action to parent compound italic = less important agent [ ] = questionable therapeutic value I =drug interactions S = side effects T = toxicity CV = cardiovascular system CNS = central nervous system Agent (trade name®) Therapeutic Use Notes E. Ishac Adrenoceptor Agonists MAOI = Monoamine oxidase inhibitors TCA = Tricyclic antidepressants Norepinephrine (Levarterenol) Hypotension, pressor agent α / β1 β3 (β2) neuronal, non-circulating, I: MAOI, TCA Epinephrine (generic) Allergic reactions, shock, CPR α / β1 β2 (β3) adrenal medulla, circulating; I: MAOI, TCA Dopamine (Intropin) Renal vasodilatation during shock α1 / β1 / D, precursor to NE, I: MAOI Isoproterenol (Isuprel) Asthma, cardiac stimulant β, synthetic, not endogenous; (↓, --) BP HR Phenylephrine (Neosynephrine) Nasal decongestant, hypotension not commonly used for hypotension; S: CV, reflex Methoxamine (Vasoxyl) Hypotension, pressor agent bradycardia Metaraminol (Aramine) Hypotension, pressor agent α, orally active; NE or DA better choice Clonidine (Catapres) Hypertension α2, ↓ cns sympathetic outflow, inhibit NE release, Guanfacine (Tenex) rebound HT; S: dry mouth, sedation, impotence. α-methyl-dopa is metabolized to α-methyl-NE (α - α 2 -methyl-dopa (Aldomet) agonist) Dobutamine (Dobutrex) CHF, cardiac stimulant β1, iv infusion, tolerance, desensitization Prenalterol Terbutaline (Brethaire) Asthma, premature labor β2-selective, Oral 1-2 hrs onset ! 4-6 hrs duration, Ritodrine (Yutopar) Premature labor Inhalation
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0184806 A1 Barlow Et Al
    US 20100184806A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0184806 A1 Barlow et al. (43) Pub. Date: Jul. 22, 2010 (54) MODULATION OF NEUROGENESIS BY PPAR (60) Provisional application No. 60/826,206, filed on Sep. AGENTS 19, 2006. (75) Inventors: Carrolee Barlow, Del Mar, CA (US); Todd Carter, San Diego, CA Publication Classification (US); Andrew Morse, San Diego, (51) Int. Cl. CA (US); Kai Treuner, San Diego, A6II 3/4433 (2006.01) CA (US); Kym Lorrain, San A6II 3/4439 (2006.01) Diego, CA (US) A6IP 25/00 (2006.01) A6IP 25/28 (2006.01) Correspondence Address: A6IP 25/18 (2006.01) SUGHRUE MION, PLLC A6IP 25/22 (2006.01) 2100 PENNSYLVANIA AVENUE, N.W., SUITE 8OO (52) U.S. Cl. ......................................... 514/337; 514/342 WASHINGTON, DC 20037 (US) (57) ABSTRACT (73) Assignee: BrainCells, Inc., San Diego, CA (US) The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system (21) Appl. No.: 12/690,915 including by stimulating or increasing neurogenesis, neuro proliferation, and/or neurodifferentiation. The disclosure (22) Filed: Jan. 20, 2010 includes compositions and methods based on use of a peroxi some proliferator-activated receptor (PPAR) agent, option Related U.S. Application Data ally in combination with one or more neurogenic agents, to (63) Continuation-in-part of application No. 1 1/857,221, stimulate or increase a neurogenic response and/or to treat a filed on Sep. 18, 2007. nervous system disease or disorder. Patent Application Publication Jul. 22, 2010 Sheet 1 of 9 US 2010/O184806 A1 Figure 1: Human Neurogenesis Assay Ciprofibrate Neuronal Differentiation (TUJ1) 100 8090 Ciprofibrates 10-8.5 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 Conc(M) Patent Application Publication Jul.
    [Show full text]
  • The Classification of Drugs and Drug Receptors in Isolated Tissues
    0031-6997/84/3603-0165$02.00/0 PHARMACOLOGICAL REVIEWS Vol. 36, No.3 Copyright © 1984 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. The Classification of Drugs and Drug Receptors in Isolated Tissues TERRY P. KENAKIN Department of Pharmacology, The Welkome Research Laboratories, Burroughs Welkome Co., Research Triangle Park, North Carolina I. Introduction 165 A. Isolated tissue and binding studies 166 II. Factors in the choice of isolated tissues 167 A. Animals 167 B. Preservation of tissue viability 167 C. Some isolated tissues from animals and man 168 D. Methods of tissue preparation 168 E. Measurement of tissue responses 172 F. Sources of variation in tissues 172 1. Heterogeneous receptor distribution 172 2. Animal maturity 173 G. Comparisons between isolated tissues 173 Downloaded from III. Equilibrium conditions in isolated tissues 173 A. Chemical degradation of drugs 174 B. Release of endogenous substances 174 C. Removal of drugs by tissues 176 1. Diffusion into isolated tissues 176 2. Drug removal processes in isolated tissues 177 by guest on June 7, 2018 3. Consequences of uptake inhibition in isolated tissues 179 IV. Quantification of responses of agonists 183 A. Dose-response curves 183 B. Drug receptor theory 184 C. The relationship between stimulus and response 185 1. Tissue response as a function of stimulus 185 2. Receptor density 188 V. Methods of drug receptor classification 188 A. Agonist potency ratios 188 B. Selective agonism 189 C. Measurement of agonist affinity and relative efficacy 192 1. Agonist affinity 192 2. Agonist efficacy 195 3. Experimental manipulation of receptor number and efficiency of stimulus response coupling 196 D.
    [Show full text]