DOCSLIB.ORG

Ep 0681833 B1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ep 0681833 B1 Europäisches Patentamt *EP000681833B1* (19) European Patent Office Office européen des brevets (11) EP 0 681 833 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 9/14, A61K 9/18 of the grant of the patent: 13.06.2001 Bulletin 2001/24 (21) Application number: 95106396.5 (22) Date of filing: 28.04.1995 (54) Nasally administrable compositions Nasal verabreichbare Mittel Compositions administrables par voie intranasale (84) Designated Contracting States: (74) Representative: Kraus, Walter, Dr. et al AT BE CH DE DK ES FR GB IT LI LU NL PT SE Patentanwälte Kraus, Weisert & Partner Thomas-Wimmer-Ring 15 (30) Priority: 11.05.1994 JP 12077894 80539 München (DE) 02.03.1995 JP 6664095 (56) References cited: (43) Date of publication of application: EP-A- 0 588 255 EP-A- 0 648 498 15.11.1995 Bulletin 1995/46 • DATABASE WPI Week 9344, Derwent (73) Proprietor: DOTT RESEARCH LABORATORY Publications Ltd., London, GB; AN 93-348353 Yokohama-shi, Kanagawa 224 (JP) ’Pharmaceutical compsn. for admin. via blood vessels - contains microcrystalline calcium (72) Inventor: Yanagawa, Akira, Med. Dr. phosphate powder as carrier for e.g. insulin’ & Yokohama-shi, Kanagawa, 224 (JP) JP-A-05 255 095 (ADVANCE K.K.) 5 October 1993 Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 0 681 833 B1 Printed by Jouve, 75001 PARIS (FR) EP 0 681 833 B1 Description 1. Field of the Invention: 5 [0001] The present invention relates to a nasally administrable composition containing a physiologically active sub- stance, which attains high stability in the form of a preparation and improved absorbability of said physiologically active substance into the body, when administered nasally. 2. Description of the Prior Art: 10 [0002] Physiologically active peptides such as calcitonin and insulin are polymers which are extensively employed for medical usage in clinical practice, due to their specific physiological activity. [0003] These physiologically active peptides, however, can little be absorbed intact from the mucous membrane of the intestine because they are likely to be decomposed with proteases existing in the digestive system or are high in 15 molecular weight and polarity. Hence, they cannot be administered orally and they can be administered only through injection. The injectable administration cannot be said to be preferable because the injection causes pain at the site of injection to patients. In addition, particularly, when the injection should be repeated at constant intervals, such pain is repeated whenever they are injected and it may often become too severe for patients to endure. Therefore, strong demand has been made to develop a method for administering the physiologically active peptide via a non-injection 20 route and, more preferably, a method which enable patients to administer it by themselves, which further should be safe, simple in administration and administrable with less frequency. [0004] As one of such methods for administering the physiologically active peptides, an aerosol in the form of a suspension, which uses a fluorinated hydrocarbon as a spouting agent, has been developed for nasally administering, for example, calcitonin. As another means for nasal administration, a spraying agent has been proposed as a nasally 25 administrable liquid preparation, which is a preparation in which calcitonin is formulated with a surface-active agent as an absorption promoter. Furthermore, recently, there have been proposed some nasally administrable powdery prep- arations having improved absorbability, which are prepared by adsorbing calcitonin onto a polysaccharide such as cellulose. [0005] On the other hand, up to now, there have been developed a great many synthetic medicaments for various 30 therapeutical purposes; however, there have not been developed into datails for nasally administrable preparations containing said medicaments. [0006] The various techniques for nasal administration, which have most recently been actively developed, are said to be in principle superior as methods for administering such physiologically active peptides as unlikely to be admin- istered orally or as well as for administering such synthetic medicaments. Since the plexus venosus develops at the 35 nasal lamina propria mucosae of the nasal cavity, the physiologically active peptide or the synthetic medicament, when administered nasally, is absorbed through the mucous membrane of the nasal cavity into the circulatory system of the body; however, nasally administrable preparations so far proposed are not satisfactory because of poor absorbability of the active ingredient or local irritation so that they are not commercially available yet. [0007] EP 648 498 discloses a physiologically active peptide composition having a physiologically active peptide 40 dispersed homogeneously in and adsorbed homogeneously onto a unique carrier and refers to compositions compris- ing hydroxyapatite. EP 648 498 is state of the art according to Article 54(3) of the European Patent Convention for the contracting states Switzerland, Liechtenstein, Germany, Spain, France, Great Britain and Italy. In order to delimit the present application from the disclosure of EP 648 498, it has been indicated in the claims for the contracting states Switzerland, Liechtenstein, Germany, Spain, France, Great Britain and Italy that the polyvalence metal carrier in the 45 claimed compositions is not hydroxyapatite. Any references to hydroxyapatite in the present description are to be understood as being of relevance for the contracting states Austria, Belgium, Denmark, Luxembourg, the Netherlands, Portugal and Sweden only. [0008] EP 588 255 discloses physiologically active petide compositions comprising a physiologically active peptide and a carrier, wherein a physiologically effective amount of said physiologically active peptide is dispersed homoge- 50 neously in and adsorbed homogeneously onto said carrier comprising a polyvalent alcohol of a polysaccharide selected from an alginic acid propylene glycol ester and a hyaluronic acid butylene glycol ester. [0009] JP 5 255 095 discloses compositions containing a microcrystalline powder of calcium phosphate as a carrier for, inter alia, insulin. The disclosed compositions are not nasally administered in powdery form, but are administered via intravenous injection of a solution containing the powder. 55 SUMMARY OF THE INVENTION [0010] The present invention has the primary object to provide a nasally administrable composition to nasally ad- 2 EP 0 681 833 B1 minister such a physiologically active peptide or other physiologically active substances as unlikely to be administered orally, with higher bioavailability and less irritation than those of other nasally administrable preparations so far pro- posed. [0011] As a result of extensive studies and researches on such nasally administrable preparations to achieve the 5 object of the present invention, it has been found that a composition, which is prepared by homogeneously dispersing the physiologically active peptide, such as calcitonin or insulin, in unique carrier, i.e. a physiologocally acceptable polyvalence metal carrier having a mean particle size of not more than 250 µ m, which has not yet been studied as a carrier for use with a nasally administrable prep- aration, and by homogeneously adsorbing it onto the carrier, is administrable via a nasal route - in other words, that 10 the composition can be applied to the mucous membrane of the nasal cavity - to thereby allow a clinically effective treatment. [0012] The term "a polyvalence metal carrier" refers to a divalence metal compound selected from the group con- sisting of aluminum compound, calcium compound, magnesium compound, silicon compound, iron compound and zinc compound. 15 [0013] Furthermore, it has been found that a nasally administrable composition of other synthetic medicaments, which is prepared by homogeneously dispersing the active substance in the same polyvalence metal carrier can also attain equal or higher clinincal effectiveness compared with those administered orally. [0014] In other words, it has been found by the present inventor that the technique of homogeneously dispersing a physiologically active peptide such as calcitonin and insulin, or other physiologically active substance in a unique carrier 20 and adsorbing said peptide or substance onto the carrier provides an equal or higher bioavailability compared with that obtained by injection or oral adminstration. [0015] As described hereinabove, the primary object of the present invention is to provide a nasally administrable composition comprising a physiologically active substance having a molecular weight of not more than 40,000 and a physiologically acceptable powdery or crystalline polyvalence metal carrier, wherein a physiologically effective amount 25 of said physiologically active substance is dispersed homogeneously in and adsorbed homogenously onto said poly- valence metal carrier, and a mean particle size of said polyvalence metal carrier is not more than 250 µm. [0016] Other objects, features and advantages of the present invention will become apparent in the course of the description of preferred
Load more

Recommended publications
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • A A–803467, 98 Absorption, Distribution, Metabolism, Elimination
    Index A Anxiety disorders, 55 A–803467, 98 APD. See Action potential duration Absorption, distribution, metabolism, Arrhythmias, 45, 46 elimination and toxicity Aryl sulfonamido indanes, 126–128, 130 (ADMET), 193 ATP-sensitive potassium channels (KATP Absorption, distribution, metabolism, channels), 61 excretion, and toxicity Atrial effective refractory period (AERP), 122, (ADMET), 68 124–126, 128, 129, 132, 138 Acetylcholine binding protein (AChBP), Autoimmune diseases, 254 61, 62, 64 AZD7009, 101 Acetylcholine receptor (AChR), 57, 64 Azimilide, 139 Action potential duration (APD), 120, 122, 123, 128, 132 B Action potentials, 243, 256, 259 Basis set, 69–70 ADME/T, 299, 304 b-Barrel membrane proteins AERP. See Atrial effective refractory period genome-wide annotation, 13 Agitoxin (AgTX), 60 machine-learning techniques Agonists, 59–61, 64 residue pair preference, 11 Alinidine, 40–42 TMBs, 10 ALS. See Amyotrophic lateral sclerosis pipeline, genomic sequences, 14 Alzheimer, 55, 61 statistical method, 9–10 AMBER, 61, 65 Bending hinge, 64 2-Amino–2-imidazolidinone, 123, 125 Benzanilide, 256–257 Ammi visnaga, 254 Benzimidazolone, 256–257 b-Amyloid peptide (Ab), 62–63, 65 Benzocaine, 140 Amyotrophic lateral sclerosis (ALS), 90, 94, Benzodiazepines, 245 101 Benzopyrane, 127–128 Anionic channel blockers Benzopyrans, 61, 246–251, 261 mechanism of action of, 329–330 Benzothiadiazine 1,1-dioxide, 252–254 Antagonists, 59, 60 Benzothiadiazines, 253 Antiarrhythmic, 65–66, 68, 99, 101 Benzothiazepine, 70 Antiarrhythmic agents Benzothiazine derivatives, 251–252 class I, 245 Benzotriazole, 256–257 class II, 245 Bestrophins, 321, 322, 330, 331 class III, 245 Big potassium channels (BK channels), Antidepressant, 65–67 256, 257 Antiepileptic, 46 Bupivacaine, 56, 58, 59, 64, 69, 140 S.P.
    [Show full text]
  • Neuroprotective Effects of Cromakalim on Cerebral Ischemia-Reperfusion (Ir) Injury and Aluminium Induced Toxicity in Rat Brain
    Innovare International Journal of Pharmacy and Pharmaceutical Sciences Academic Sciences ISSN- 0975-1491 Vol 6, Issue 6, 2014 Original Article NEUROPROTECTIVE EFFECTS OF CROMAKALIM ON CEREBRAL ISCHEMIA-REPERFUSION (IR) INJURY AND ALUMINIUM INDUCED TOXICITY IN RAT BRAIN *1PITHADIA ANAND BHARAT KUMAR, 2SHITAL PANCHAL *1Department of Pharmacology, Parul Institute of Pharmacy, Vadodara,2 Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India. Email: [email protected] Received: 29 Apr 2014 Revised and Accepted: 28 May 2014 ABSTRACT Objective: Preclinical studies have demonstrated that potassium channel openers show a neuroprotective effect on cerebral ischemia-reperfusion (IR) injury in rats. However, their mechanism of action and effects in brain stroke related disorders such as Alzheimer’s disease (AD) remain poorly understood. Hence present study was done to investigate the prophylactic use of the adenosine triphosphate-sensitive (ATP) potassium channel opener cromakalim on neurological function in rats with cerebral IR injury and its related disorders AD. Methods: Male Wistar rats were randomly assigned to 6 groups (n = 36): Normal control, aluminium chloride(AlCl3) control, AlCl3 Sham operated, ischemia reperfusion (IR) control, AlCl3-IR control and AlCl3-IR with cromakalim treatment. Cromakalim10 mg/kg intra peritonially (i.p.) was administered daily for 42 days in middle cerebral artery occluded rats treated with AlCl3. At 24 hours post-surgery, neurological score, brain hemisphere weight difference, brain acetylcholinestarase level, lipid peroxidation, Na+/K+ ATPase pump activity and super oxide dismutase level were measured. Results: Following cerebral ischemia-reperfusion injury along with aluminium chloride, neurological score,brain hemisphere weight difference, brain acetylcholinestarase level, malondialdehyde levels were significantly high while Na+/K+ ATPase pump activity and super oxide dismutase(SOD) levels were significantly lower in diseased animals (P < 0.05).
    [Show full text]
  • L:\0901 with Peru\0901PHARMAPPX.Wpd
    Harmonized Tariff Schedule of the United States (2009) (Rev. 1) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2009) (Rev. 1) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACEXAMIC ACID 57-08-9 ABAFUNGIN 129639-79-8 ACICLOVIR 59277-89-3 ABAMECTIN 65195-55-3 ACIFRAN 72420-38-3 ABANOQUIL 90402-40-7 ACIPIMOX 51037-30-0 ABAPERIDONE 183849-43-6 ACITAZANOLAST 114607-46-4 ABARELIX 183552-38-7 ACITEMATE 101197-99-3 ABATACEPT 332348-12-6 ACITRETIN 55079-83-9 ABCIXIMAB 143653-53-6 ACIVICIN 42228-92-2 ABECARNIL 111841-85-1 ACLANTATE 39633-62-0 ABETIMUS 167362-48-3 ACLARUBICIN 57576-44-0 ABIRATERONE 154229-19-3 ACLATONIUM NAPADISILATE 55077-30-0 ABITESARTAN 137882-98-5 ACODAZOLE 79152-85-5 ABLUKAST 96566-25-5 ACOLBIFENE 182167-02-8 ABRINEURIN 178535-93-8 ACONIAZIDE 13410-86-1 ABUNIDAZOLE 91017-58-2 ACOTIAMIDE 185106-16-5 ACADESINE 2627-69-2 ACOXATRINE 748-44-7 ACAMPROSATE 77337-76-9 ACREOZAST 123548-56-1 ACAPRAZINE 55485-20-6
    [Show full text]
  • Pharmaceutical Appendix to the Harmonized Tariff Schedule
    Harmonized Tariff Schedule of the United States Basic Revision 3 (2021) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States Basic Revision 3 (2021) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,329,697 B2 Garbaccio Et Al
    US008329697B2 (12) United States Patent (10) Patent No.: US 8,329,697 B2 Garbaccio et al. (45) Date of Patent: Dec. 11, 2012 (54) IMIDIZO 1.2-APYRAZINES USEFUL AS (56) References Cited AHCY HYDROLASE INHIBITORS U.S. PATENT DOCUMENTS (75) Inventors: Robert M. Garbaccio, Lansdale, PA 4,507,294 A 3, 1985 Bristol et al. (US); Antonella Converso, Elkins Park, 56.6 f 3.3: Ret , al PA (US); Mark E. Fraley, North Wales, 4. W w Wa (a. PA (US); Timothy J. Hartingh, Blue 2004/0204429 A1 10, 2004 Yuan Bell, PA (US) FOREIGN PATENT DOCUMENTS WO WO 2009/108546 * 9/2009 (73) Assignee: Merck Sharp & Dohme Corp., OTHER PUBLICATIONS Rahway, NJ (US) Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205.* (*) Notice: Subject to any disclaimer, the term of this Hackam, et al. JAMA, 296(14), 2006, 1731-1732.* patent is extended or adjusted under 35 * cited b U.S.C. 154(b) by 163 days. c1ted by examiner Primary Examiner — Douglas MWillis (21) Appl. No.: 12/811,911 (74) Attorney, Agent, or Firm — Kenrick L. Vidale; John C. Todaro (22) PCT Filed: Feb. 18, 2009 (57) ABSTRACT (86). PCT No.: PCT/US2O09/034344 The present invention is directed to AHCY inhibitors of for mula (I) which are useful in the treatment of diseases charac S371 (c)(1), terized by high homocysteine levels, such as Alzheimer's (2), (4) Date: Jul. 7, 2010 disease. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of (87) PCT Pub. No.: WO2009/108546 the compounds and compositions in the treatment of diseases PCT Pub.
    [Show full text]
  • Effect of Niflumic Acid on Noradrenaline-Induced Contractions of the Rat Aorta D.N
    Brifish Journal of Pharmacology (1996) 118, 1065-1071 1996 Stockton Press All rights reserved 0007-1188/96 $12.00 0 Effect of niflumic acid on noradrenaline-induced contractions of the rat aorta D.N. Criddle, R. Soares de Moura, l*I.A. Greenwood & *W.A. Large Departmento de Farmacologia, Centro Biomedico - IB, Universidade do Estado do Rio de Janeiro, Brasil and *Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE 1 The effects of niflumic acid, an inhibitor of calcium-activated chloride channels, were compared with the actions of the calcium channel antagonist nifedipine on noradrenaline-evoked contractions in isolated preparations of the rat aorta. 2 The cumulative concentration-effect curve to noradrenaline (NA) was depressed by both nifedipine and niflumic acid in a reversible and concentration-dependent manner. The degree of inhibition of the maximal contractile response to NA (1 gM) produced by 10 gM niflumic acid (38%) was similar to the effect of 1 gM nifedipine (39%). 3 Contractions to brief applications (30 s) of 1 pM NA were inhibited by 55% and 62% respectively by 10 gM niflumic acid and 1 gM nifedipine. 4 In the presence of 0.1 Mm nifedipine, niflumic acid (10 gM) produced no further inhibition of the NA- evoked contractions. Thus, the actions of niflumic acid and nifedipine were not additive. 5 In Ca-free conditions the transient contraction induced by 1 gM NA was not inhibited by niflumic acid (10 Mm) and therefore this agent does not reduce the amount of calcium released from the intracellular store or reduce the sensitivity of the contractile apparatus to calcium.
    [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]
  • Potassium Channel Kcsa
    Potassium Channel KcsA Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions. Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly and selectively. Biologically, these channels act to set or reset the resting potential in many cells. In excitable cells, such asneurons, the delayed counterflow of potassium ions shapes the action potential. By contributing to the regulation of the action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias. Potassium channels may also be involved in maintaining vascular tone. www.MedChemExpress.com 1 Potassium Channel Inhibitors, Agonists, Antagonists, Activators & Modulators (+)-KCC2 blocker 1 (3R,5R)-Rosuvastatin Cat. No.: HY-18172A Cat. No.: HY-17504C (+)-KCC2 blocker 1 is a selective K+-Cl- (3R,5R)-Rosuvastatin is the (3R,5R)-enantiomer of cotransporter KCC2 blocker with an IC50 of 0.4 Rosuvastatin. Rosuvastatin is a competitive μM. (+)-KCC2 blocker 1 is a benzyl prolinate and a HMG-CoA reductase inhibitor with an IC50 of 11 enantiomer of KCC2 blocker 1. nM. Rosuvastatin potently blocks human ether-a-go-go related gene (hERG) current with an IC50 of 195 nM. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 1 mg, 5 mg (3S,5R)-Rosuvastatin (±)-Naringenin Cat. No.: HY-17504D Cat. No.: HY-W011641 (3S,5R)-Rosuvastatin is the (3S,5R)-enantiomer of (±)-Naringenin is a naturally-occurring flavonoid.
    [Show full text]
  • WHO-EMP-RHT-TSN-2018.1-Eng.Pdf
    WHO/EMP/RHT/TSN/2018.1 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.
    [Show full text]
  • PJP5'2004.Vp:Corelventura
    Copyright © 2004 by Institute of Pharmacology Polish Journal of Pharmacology Polish Academy of Sciences Pol. J. Pharmacol., 2004, 56, 499508 ISSN 1230-6002 “…I’ll tell you all my ideas about Looking Glass House. First, there’s the room you can see through the glass – that’s just the same as our drawing room, only the thing go other way… Well then, the books are something like our books, only the words go the wrong way; …I wonder if they’d give you milk in there? Perhaps Looking-Glass milk isn’t good to drink…” “Through the Looking Glass” Lewis Caroll (1832–1898) REVIEW INFLUENCE OF THE ABSOLUTE CONFIGURATION ON PHARMACOLOGICAL ACTIVITY OF ANTIHYPERTENSIVE AND ANTIARRHYTHMIC DRUGS Katarzyna Kulig, Piotr Nowicki, Barbara Malawska Department of Pharmaceutical Chemistry, Medical College, Jagiellonian University, Medyczna 9, PL 30-688 Kraków, Poland Influence of the absolute configuration on pharmacological activity of antihypertensive and antiarrhythmic drugs. K. KULIG, P. NOWICKI, B. MALAWSKA. Pol. J. Pharmacol., 2004, 56, 499–508. Chirality is a fundamental property of biological systems and reflects the underlying asymmetry of matter. Interactions of drugs with receptors, en- zymes or binding sites have long been known to be stereoselective, and it is increasingly recognized that both pharmacodynamic and pharmacokinetic events contribute to the overall clinically observed stereoselectivity. The pharmacological activity may reside only in one enantiomer, while the second one may be inactive or have desirable or undesirable activity. Two isomers may be nearly identical both in qualitative and quantitative as- pects of pharmacological activity. The activity of particular enantiomers may differ only at the quantitative level.
    [Show full text]
  • (DTX) 217 – Selectivity 219 A-278637
    467 Index a – pentylenetetrazol 357 ff. a interaction domain 71 – picrotoxin 357 a1 subunit 69 ff. antiepileptic drugs, receptor sites 9 a2-d subunit 57, 69 ff. antiepileptics 87 a-Dendrotoxin (DTX) 217 anxiety 369 – selectivity 219 – canopy test 369 ff. A-278637 344 ff. apamin 242, 244, 326 f. A- 411873 323 apoptosis 237 acetylcholine receptor deficiency 408 –Fas receptor 237 AChR 410 – mitochondria 237 action potential 44, 55 aryloxindole 321 adipocytes 244 ff. arylpyrrole 323 – brown fat 244 asthma 324 – glucose transporter 244 ATP-sensitive potassium channel KATP 335, – white fat 244 385 afterhyperpolarization 314 atrial effective refractory period (AERP) Agenelopsis aperta 131 291 alkaloid 319, 328 atrial fibrillation 276 ALMOND modul 432 ff. atrial vulnerability 291 Alzheimer’s disease 317 autism 396 ambasilide 278 autoantibodies 238 amiloride-sensitive epithelial sodium autoimmune diseases 247 ff. channel 397 autosomal dominant 4-aminopyridine 222 – juvenile myoclonic epilepsy 412 amiodarone 29, 278 – nocturnal frontal lobe epilepsy 410 amitriptyline, NaV blocking activity 186 auxiliary subunit in amlodipine 89 ff. –Kvb 11 amygdala-kindling model 357 ff., 361 – KChIp1-4 11 anandamide 91 – minK 11 ancillary calcium channel subunits 69 ff., auxiliary subunits 77 –Cava210 Andersen-Tawil syndrome 383 –Cavb 10 anesthetics 87 –Cavd 10 anosmia 251 –Cavg 10 antiarrhythmic drugs 9, 278 –Navb19 anticonvulsant –ofK+ channels 198 – amygdala-kindling 357 ff. AVE0118 287, 289 –6Hz model 361 azaindole 323 – maximal electroshock 357 ff. azimilide 278 Voltage-Gated Ion Channels as Drug Targets. Edited by D. Triggle Copyright c 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-31258-7 468 Index b – dialkyl-dipeptidylamines 132 b cell rest 341 – dihydropyridines 139 ff.
    [Show full text]