DOCSLIB.ORG

N-Ethoxyethylpiperidine, Trimecaine and Piromecaine Based Ionic Compounds: Synthesis and Prediction of Biological Activity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
N-Ethoxyethylpiperidine, Trimecaine and Piromecaine Based Ionic Compounds: Synthesis and Prediction of Biological Activity International Journal of Chemical Engineering and Applications, Vol. 8, No. 3, June 2017 N-ethoxyethylpiperidine, Trimecaine and Piromecaine Based Ionic Compounds: Synthesis and Prediction of Biological Activity D. S. Zolotareva, A. A. Basharimova, S. Bayazit, V. K. Yu, and A. G. Zazybin anti-arrhythmic activity with no teratogenic, embriotoxic, Abstract—Herein we report on the synthesis of new ionic mutagenic and allergic effects [7]. Trimecaine which we used compounds based on N-ethoxyethylpiperidine, trimecaine and in our research as a parent compound nowadays has been piromecaine, obtained via N-alkylation with alkyl halides. The applied as a local anesthetic and antiarrhythmic and in cardio combination of piperidine ring, secondary amine group, trimecaine and piromecaine in form of a base with different surgery [8], [9]. Piromecaine also shows local anesthetic and alkyl radicals bring to molecule new biological activity and/or antiarrhythmic activity [10], [11]. To define the range of reduce toxic effects of parent compounds. The potential biological activity of new synthesized compounds we used pharmacological activity and potential toxic effects of the Pass online service (Prediction of Activity Spectra for obtained compounds were predicted with PASS online service Substances) [12], which helps to predict biological and (Prediction of Activity Spectra for Substances) showing pharmacological effects, action mechanisms and also toxicity cardiotonic, antiarrhythmic and spasmolytic potential activities. The dependence of the potential activity on the nature of and adverse impact of compound, for example as in [13] – substituent was compared. These novel ionic compounds can be [15]. In this manuscript we report some methods for the applied for synthesis of ionic compounds and drug candidates. synthesis of new ionic compounds and study of their potential biological activity. Index Terms—Ionic liquids, N-ethoxyethylpiperidine, PASS prediction, piromecaine, trimecaine. II. SYNTHESIS OF THE IONIC COMPOUNDS BASED ON N-ETHOXYETHYLPIPERIDINE I. INTRODUCTION The acetylene alcohol compound One of the main strategies of the search for new 1-(2-ethoxyethyl)-4-ethynylpiperidin-4-ol was chosen as a biologically active compounds in the last decade is a starting compound for the synthesis of new ionic substances - combination of two or more pharmacophore groups in one drug candidates. 1-(2-ethoxyethyl)-4-ethynylpiperidin-4-ol compound [1]. In this manusctipt we are now taking this was synthesized as hydrochloride by the Favorskii reaction strategy to a relatively new class of organic compounds - ionic from 1-(2-ethoxyethyl)-4-piperidone according to the liquids. One well-known example of a successful transition well-known procedure [16]. For the purpose of new ionic from the molecular (non-ionic) form of the drug to the ionic compounds synthesis it was transferred into the form of a base liquid form is lidocaine docusate [2] – an ionic form of and then undergone the process of alkylation with alkyl lidocaine is better absorbed by the organism and has a halides. combination of analgesic and emollient properties. The The general procedure for the alkylation is a treating of presence of piperidine ring and/or secondary amide group 1-(2-ethoxyethyl)-4-ethynylpiperidin-4-ol with acetonitrile appears to be very interesting in terms of the search for new solution of corresponding alkyl halide. The mixture is taken biologically active compounds [3]-[5]. Especially it worth under reflux for 0.5 – 12 hours. Then the obtained compound mentioning the piperidine derivatives those include the is purified with different methods. general structural part N-ethoxyethylpiperidine, where the At first the ionic compound based on ethoxyethyl substituent plays an important role in the 1-(2-ethoxyethyl)-4-acetyl-4-hydroxypiperidine and methyl occurrence of biological activity [6]. N-ethoxyethylpiperidine iodide - 1-(2-ethoxyethyl) derivative: -4-ethynyl-4-hydroxy-1-methylpiperidine iodide was 1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxy-piperidine.hydroc synthesized (1) (Fig. 1). Synthesis was carried out in hloride known as kazcaine shows anesthetic and acetonitrile medium under the reflux for 1 hour. Manuscript received January 20, 2017; revised May 6, 2017. This work supported by Ministry of Education and Science of Republic of Kazakhstan under Grants 1318/GF4, 1752/GF4, 0650/GF4 and 0251/PTF. D. S. Zolotareva, A. A. Basharimova, S. Bayazit, A. G. Zazybin are with the Center of Chemical Engineering, Kazakh-British Technical University, 59 Tole-bi street, Almaty, 050000, Kazakhstan (e-mail: [email protected], [email protected], [email protected], [email protected]). V. K. Yu is with Institute of Chemical Sciences named after A.B. Fig. 1. Synthesis of Bekturov, Walikhanov Str., 106, Almaty 050010, Kazakhstan (e-mail: 1-(2-ethoxyethyl)-4-ethynyl-4-hydroxy-1-methylpiperidinium iodide (1). [email protected]). doi: 10.18178/ijcea.2017.8.3.661 226 International Journal of Chemical Engineering and Applications, Vol. 8, No. 3, June 2017 Purification of the product was carried out by gastric arrhythmia, at cardiac glycoside intoxication, at acute crystallization from acetone. In the IR spectrum of the product myocardial infarct [18]. At the same time, ionic compounds the shift of vibration bands (cm-1) of the functional groups in based on them are not well studied, especially in terms of their comparison to the starting material was observed: 3266 (O-H); pharmacological activity. In this section, we report on the 2109 (CC), 1276, 1192, 1173 (C-O), 859 (C-N) for the synthesis of ionic compounds based on trimecaine and product (1) and 3238 (O-H); 2097 (CC), 1288, 1257, 1226 piromecaine and study of their physical and chemical (C-O), 880 (C-N) for the initial characteristics. 1-(2-ethoxyethyl)-4-ethynylpiperidin-4-ol. In both cases, the pharmaceutical substance was taken in The mass spectrum of the alkylation product was recorded the hydrochloride form. Trimecaine represents the and the signal with mass 212.2, corresponding the cationic hydrochloride of 2,4,6-trimetilanilide of part of 1- (2-ethoxyethyl) N,N-diethylamine-acetic acid and piromecaine represents the -4-ethynyl-4-hydroxy-1-methyl-piperidinium iodide (1) was hydrochloride of 2,4,6- detected. trimethylanilide-1-butyl-pyrrolidine-2-carboxylic acid. For the synthesis of ionic compound with ethyl moiety at Structures are shown in Fig. 3. the nitrogen atom 1-(2-ethoxyethyl)-4-ethynylpiperidin-4-ol was reacted with ethyl iodide (Fig. 2). The reaction was performed for 3.5 hours under the reflux in acetonitrile medium to get product (2). Fig. 3. Structure of hydrochloride form of trimecaine (left) and piromecaine (right). To carry out the alkylation reaction trimecaine hydrochloride was transferred into the form of a base by reaction with potassium carbonate, the product was isolated Fig. 2. Synthesis of 1- (2-ethoxyethyl) -4-ethynyl-4-hydroxy-1-ethylpiperidinium iodide (2). from the aqueous solution by extraction with benzene. Firstly we synthesized (Fig. 4) N, After removal of the solvent the yellow liquid was obtained, N-diethyl-2-(mesitylamino)-N-methyl-oxoethanaminium that doesn’t harden at a temperature -190C, indicating the iodide (3) by alkylation of trimecaine with methyl iodide. formation of the ionic liquid. The IR spectrum of the After mixing of acetonitrile solutions of reagents the reaction alkylation product shows vibration bands (cm-1) of the mixture was left at room temperature for 24 hours. Then the functional groups different from the starting material: 3239 solution was heated to reflux and thereafter was concentrated (O-H); 2097 (CC) 1263, 1227 (C-O), 879 (C-N). twice. The obtained upon cooling white crystals were In the mass spectrum of the alkylation product the signal crystallized from acetone:hexane 13:1 mixture. with mass 226.2 was detected, corresponding to the cationic part of 1-(2-ethoxyethyl) -4-ethynyl-4-hydroxy-1-ethyl-piperidinium iodide (2). In the proton spectrum of the sample the peaks of the methyl groups are observed at 1.17 and 1.40 ppm. The peaks at 2.23-2.52 and 3.77-3.91 ppm belong to the equivalent Fig. 4. Synthesis of N, protons of heterocycle. Singlet with chemical shift at 2.75 N-diethyl-2-(mesitylamino)-N-methyl-oxoethanaminium iodide (3). ppm can be attributed to the proton at sp-hybridized carbon atom. Methylene protons resonate at 3.49-3.86 ppm. The purified product was characterized by IR, NMR In the carbon spectrum most highfield peaks at 8.65 and spectroscopy. In the IR spectrum a characteristic absorption band of the amide group is observed. 15.20 ppm can be attributed to the methyl carbons. 1 Symmetrically arranged atoms of the piperidine ring resonate In the H NMR spectrum the protons of methyl groups at 33.21 and 67.33 ppm. Methylene atoms give signals with resonate at 1.28, 2.08, 2.19 and 3.15 ppm. Methylene the chemical shifts of 56.20, 62.76 and 63.82 ppm. The provides peaks at 3.52 and 4.27 ppm. Peak with chemical shift resonance lines at 74.41 and 84.85 ppm correspond to of 6.87 ppm corresponds to protons of benzene ring. The sp-hybridized carbon atoms. high-frequency peak at 9.81 ppm can be attributed to a proton of an amide group. In the carbon spectrum the signals of the methyl groups are III. SYNTHESIS OF IONIC COMPOUNDS BASED ON found at 8.37-48.46 ppm. Methylene carbons resonates at TRIMECAINE AND PIROMECAINE 57.94 and 59.05 ppm. Low-intensity peaks at 129.02-136.78 ppm refer to the carbon atoms of the benzene ring. The atom Trimecaine and piromecaine are widely used drugs having of the carbonyl group gives a peak at 162.52 ppm. Here and local anesthetic and antiarrhythmic activity [17] find for the further compounds mentioned in this paper the application in ophthalmology and otolaryngology, for assignment of the signals was carried out with the anesthesia in endoscopic studies; intravenously appointed at involvement of the two-dimensional COSY spectroscopy and 227 International Journal of Chemical Engineering and Applications, Vol.
Load more

Recommended publications
  • WO 2016/081643 Al 26 May 2016 (26.05.2016) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/081643 Al 26 May 2016 (26.05.2016) W P O P C T (51) International Patent Classification: (71) Applicant (for AL, AT, BE, BG, CH, CN, CY, CZ, DE, DK, C07K 16/28 (2006.01) C12N 15/13 (2006.01) EE, ES, FI, FR, GB, GR, HR, HU, IE, IN, IS, IT, LT, LU, C07K 16/40 (2006.01) A61K 39/395 (2006.01) LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, C07K 16/46 (2006.01) A61P 25/00 (2006.01) SM, TR only): F. HOFFMANN-LA ROCHE AG [CH/CH]; Grenzacherstrasse 124, 4070 Basel (CH). (21) International Application Number: PCT/US20 15/06 1405 (72) Inventors: ZHANG, Yin; 1 DNA Way, South San Fran cisco, California 94080 (US). ZUCHERO, Joy Yu; 1 (22) International Filing Date: DNA Way, South San Francisco, California 94080 (US). 18 November 2015 (18.1 1.2015) ATWAL, Jasvinder; 1 DNA Way, South San Francisco, (25) Filing Language: English California 94080 (US). COUCH, Jessica; 1 DNA Way, South San Francisco, California 94080 (US). DENNIS, (26) Publication Language: English Mark S.; 1 DNA Way, South San Francisco, California (30) Priority Data: 94080 (US). ERNST, James A.; 1 DNA Way, South San 62/081,827 19 November 2014 (19. 11.2014) US Francisco, California 94080 (US). WATTS, Ryan J.; 1 DNA Way, South San Francisco, California 94080 (US). (71) Applicant (for all designated States except AL, AT, BE, LAZAR, Gregory A.; 1 DNA Way, South San Francisco, BG, BN, CH, CN, CY, CZ, DE, DK, EE, ES, FI, FR, GB, California 94080 (US).
    [Show full text]
  • 761066Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 761066Orig1s000 CLINICAL REVIEW(S) Medical Officer’s Review of BLA 761066 Division of Dermatology and Dental Products Type: Biosimilar 351(k) Correspondence date: 25-MAY-2017 Serial Amendment: 000 CDER Stamp date: 25-MAY-2017 Supporting Document Number: 001 Review Date: 19-MAR-2018 Applicant: Samsung Bioepis Co., Ltd. 107 Cheomdan-daero, Yeonsu-gu Incheon, Republic of Korea 21987 Drug: SB4, a proposed biosimilar to U.S.-licensed Enbrel (etanercept) Route of Administration: Subcutaneous Dosage Form: Single-use pre-filled syringes: 50 mg/1.0 mL (50 mg/mL); 25 mg/0.5 mL (50 mg/mL) Pharmacologic Category: 1-235-tumor necrosis factor receptor (human) fusion protein with 236-467-immunoglobulin Gi (human γ1-chain Fc fragment), dimer Proposed Indications: 1) Rheumatoid Arthritis (RA) in combination with methotrexate: Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active disease. 2) Polyarticular Juvenile Idiopathic Arthritis Reducing signs and symptoms of moderately to severe active polyarticular juvenile idiopathic arthritis (JIA) in patients 2 years and older and weigh 63 kg (138 pounds) or more. 3) Ankylosing Spondylitis (AS): Reducing signs and symptoms in patients with active disease 4) Psoriatic Arthritis (PsA): Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function. 5) Plaque Psoriasis (PsO): Treatment of patients 4 years and older with chronic moderate or severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Project Manager: Barbara Gould Team Leader: David Kettl, MD Medical Officer: Gary Chiang, MD, MPH.
    [Show full text]
  • Local Anaesthetic Infiltration for Peri-Operative Pain Control in Total
    Marques et al. BMC Musculoskeletal Disorders 2014, 15:220 http://www.biomedcentral.com/1471-2474/15/220 RESEARCH ARTICLE Open Access Local anaesthetic infiltration for peri-operative pain control in total hip and knee replacement: systematic review and meta-analyses of short- and long-term effectiveness Elsa MR Marques1*, Hayley E Jones1, Karen T Elvers2, Mark Pyke3, Ashley W Blom2 and Andrew D Beswick2 Abstract Background: Surgical pain is managed with multi-modal anaesthesia in total hip replacement (THR) and total knee replacement (TKR). It is unclear whether including local anaesthetic infiltration before wound closure provides additional pain control. Methods: We performed a systematic review of randomised controlled trials of local anaesthetic infiltration in patients receiving THR or TKR. We searched MEDLINE, Embase and Cochrane CENTRAL to December 2012. Two reviewers screened abstracts, extracted data, and contacted authors for unpublished outcomes and data. Outcomes collected were post-operative pain at rest and during activity after 24 and 48 hours, opioid requirement, mobilisation, hospital stay and complications. When feasible, we estimated pooled treatment effects using random effects meta-analyses. Results: In 13 studies including 909 patients undergoing THR, patients receiving local anaesthetic infiltration experienced a greater reduction in pain at 24 hours at rest by standardised mean difference (SMD) −0.61 (95% CI −1.05, −0.16; p = 0.008) and by SMD −0.43 (95% CI −0.78 −0.09; p = 0.014) at 48 hours during activity. In TKR, diverse multi-modal regimens were reported. In 23 studies including 1439 patients undergoing TKR, local anaesthetic infiltration reduced pain on average by SMD −0.40 (95% CI −0.58, −0.22; p < 0.001) at 24 hours at rest and by SMD −0.27 (95% CI −0.50, −0.05; p = 0.018) at 48 hours during activity, compared with patients receiving no infiltration or placebo.
    [Show full text]
  • This Is the Author's Version of a Work That Was Accepted for Publication In
    NOTICE: this is the author’s version of a work that was accepted for publication in the European Journal of Medicinal Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in the European Journal of Medicinal Chemistry, Vol. 63 (2013). DOI: 10.1016/j.ejmech.2013.02.003 Synthesis, local anaesthetic and antiarrhythmic activities of N-alkyl derivatives of proline anilides Dmitrii V. Kalinin,a Vladimir I. Pantsurkin,a Boris Ya. Syropyatov,a Svetlana A. Kalinina,a Irina P. Rudakova,a Mikhail I. Vakhrina and Anton V. Dolzhenkob,c* a Perm State Pharmaceutical Academy, 2 Polevaya Street, Perm 614990, Russian Federation b Jeffrey Cheah School of Medicine and Health Sciences, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, Selangor 46150, Malaysia c School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987 Perth, Western Australia 6845, Australia Corresponding author. Tel.: +61-8-9266-3747; fax: +61-8-9266-2769. E-mail addresses: [email protected]; [email protected]; [email protected] (A. V. Dolzhenko) Abstract We describe here the design, synthesis and evaluation of in vivo local anaesthetic and antiarrhythmic activities of a series of N-alkylproline anilides. Most of the compounds demonstrated surface anaesthetic activity higher than that of lidocaine, ropivacaine and bupivacaine. We established that the local anaesthetic activity was sensitive to structural variations in the substitution pattern at the aromatic ring and the type of alkyl group at the proline nitrogen atom.
    [Show full text]
  • Pharmacology
    STATE ESTABLISHMENT «DNIPROPETROVSK MEDICAL ACADEMY OF HEALTH MINISTRY OF UKRAINE» V.I. MAMCHUR, V.I. OPRYSHKO, А.А. NEFEDOV, A.E. LIEVYKH, E.V.KHOMIAK PHARMACOLOGY WORKBOOK FOR PRACTICAL CLASSES FOR FOREIGN STUDENTS STOMATOLOGY DEPARTMENT DNEPROPETROVSK - 2016 2 UDC: 378.180.6:61:615(075.5) Pharmacology. Workbook for practical classes for foreign stomatology students / V.Y. Mamchur, V.I. Opryshko, A.A. Nefedov. - Dnepropetrovsk, 2016. – 186 p. Reviewed by: N.I. Voloshchuk - MD, Professor of Pharmacology "Vinnitsa N.I. Pirogov National Medical University.‖ L.V. Savchenkova – Doctor of Medicine, Professor, Head of the Department of Clinical Pharmacology, State Establishment ―Lugansk state medical university‖ E.A. Podpletnyaya – Doctor of Pharmacy, Professor, Head of the Department of General and Clinical Pharmacy, State Establishment ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ Approved and recommended for publication by the CMC of State Establishment ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ (protocol №3 from 25.12.2012). The educational tutorial contains materials for practical classes and final module control on Pharmacology. The tutorial was prepared to improve self-learning of Pharmacology and optimization of practical classes. It contains questions for self-study for practical classes and final module control, prescription tasks, pharmacological terms that students must know in a particular topic, medical forms of main drugs, multiple choice questions (tests) for self- control, basic and additional references. This tutorial is also a student workbook that provides the entire scope of student’s work during Pharmacology course according to the credit-modular system. The tutorial was drawn up in accordance with the working program on Pharmacology approved by CMC of SE ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ on the basis of the standard program on Pharmacology for stomatology students of III - IV levels of accreditation in the specialties Stomatology – 7.110105, Kiev 2011.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,993,836 Castillo (45) Date of Patent: Nov.30, 1999
    USOO5993836A United States Patent (19) 11 Patent Number: 5,993,836 Castillo (45) Date of Patent: Nov.30, 1999 54 TOPICAL ANESTHETIC FORMULATION 5,002,974 3/1991 Geria ....................................... 514/782 5,332,576 7/1994. Mantelle . ... 424/443 76 Inventor: James G. Castillo, 15412-15'St., Lutz, 5,585,398 12/1996 Ernst ....................................... 514/537 Fla. 33549 Primary Examiner Thurman K. Page ASSistant Examiner William E. Benston, Jr. 21 Appl. No.: 09/067,948 Attorney, Agent, or Firm-Pendorf & Cutliff 22 Filed: Apr. 28, 1998 57 ABSTRACT 51 Int. Cl. ................................ A61K 6/00; A61K 7/00 A topical, transdermal anesthetic comprising a eutectic mix 52 U.S. Cl. .......................... 424/401; 424/443; 424/435; ture of, preferably, lidocaine and prilocaine in a ratio of 424/485 about 3:1 by weight, incorporated within a lipophilic base. 58 Field of Search ..................................... 424/401, 443, In addition to the property of rapid-onset, the formulation of 424/435, 485, 484, 450, 486 the present invention has high Storage Stability and is leSS restricted by dosage limitations of other prilocaine 56) References Cited containing transdermal anesthetics and is, advantageously, U.S. PATENT DOCUMENTS not dependent upon occlusive dressing for optimal transder mal absorption. 4,529,601 7/1985 Broberg et al. ......................... 514/626 4.562,060 12/1985 Broberg et al. ........................... 424/28 20 Claims, No Drawings 5,993,836 1 2 TOPCAL ANESTHETIC FORMULATION of risks associated with parenteral treatment, elimination of the inconveniences of parenteral treatment; and elimination BACKGROUND OF THE INVENTION of gastrointestinal irritation resulting from exposing the 1.
    [Show full text]
  • Percutaneous Absorption of Disopyramide, Lidocaine and Trimecaine
    Volume 141, 1998 31 PERCUTANEOUS ABSORPTION OF DISOPYRAMIDE, LIDOCAINE AND TRIMECAINE Jan Příborskýa,b,*, Katsuya Kikuchic, Kozo Takayamac, Tsuneji Nagaic a Glaxo W ellcome s.r.o., K Žižkovu 4, 190 00 Prague, Czech Republic b Institute of Pharmacology, Faculty of Medicine, Palacký University, Hněvotínská 3, 77 515 Olomouc, Czech Republic c Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142, Japan Received December 10,1997 Key words: Antiarrhytmic drugs / Penetration enhancer / Cyclic monoterpenes Promoting effect of cyclic monoterpenes on percutaneous absorption of antiarrhytmic drugs disopyramide, lidocaine and trimecaine was investigated in the rats. Laurocapram (Azone) was used as a standard comparator of penetration enhance- ment. The absorption of trimecaine was significantly enhanced by addition of limonene, trans-p-menthane and Azone in 1% concentration. Lidocaine and disopyramide penetrated across the skin only when 1% of limonene was used. Other cyclic monoterpenes showed no effect on percutaneous absorption of examined drugs. INTRODUCTION ride which was generous gift from Sanitas (Říčany u Pra- hy, Czech Republic). Following cyclic monoterpenes we- Previous studies performed in our laboratory proved re used: hydrocarbons – limonene and trans-p-menthane, that several antirheumatics are suitable candidates for alcohols – menthol, ketones – menthone and ethers – percutaneous drug formulations1,2. Percutaneous absorp- cineole, all by Tokyo Chemical Industries Co., Ltd. (To- tion of drugs can be enhanced by means of cyclohexanone kyo, Japan). Laurocapram (Azone) was supplied by Su- derivatives1, cyclic monoterpenes 2 and other penetration misho-Nelson Co., Ltd. (Osaka Japan). Carboxyvinyl enhancers like Azone, DMSO, pyrrolidones3 or dioxola- polymer, marketed as „hiviswako 105“ was supplied from nes4.
    [Show full text]
  • 2021 Equine Prohibited Substances List
    2021 Equine Prohibited Substances List . Prohibited Substances include any other substance with a similar chemical structure or similar biological effect(s). Prohibited Substances that are identified as Specified Substances in the List below should not in any way be considered less important or less dangerous than other Prohibited Substances. Rather, they are simply substances which are more likely to have been ingested by Horses for a purpose other than the enhancement of sport performance, for example, through a contaminated food substance. LISTED AS SUBSTANCE ACTIVITY BANNED 1-androsterone Anabolic BANNED 3β-Hydroxy-5α-androstan-17-one Anabolic BANNED 4-chlorometatandienone Anabolic BANNED 5α-Androst-2-ene-17one Anabolic BANNED 5α-Androstane-3α, 17α-diol Anabolic BANNED 5α-Androstane-3α, 17β-diol Anabolic BANNED 5α-Androstane-3β, 17α-diol Anabolic BANNED 5α-Androstane-3β, 17β-diol Anabolic BANNED 5β-Androstane-3α, 17β-diol Anabolic BANNED 7α-Hydroxy-DHEA Anabolic BANNED 7β-Hydroxy-DHEA Anabolic BANNED 7-Keto-DHEA Anabolic CONTROLLED 17-Alpha-Hydroxy Progesterone Hormone FEMALES BANNED 17-Alpha-Hydroxy Progesterone Anabolic MALES BANNED 19-Norandrosterone Anabolic BANNED 19-Noretiocholanolone Anabolic BANNED 20-Hydroxyecdysone Anabolic BANNED Δ1-Testosterone Anabolic BANNED Acebutolol Beta blocker BANNED Acefylline Bronchodilator BANNED Acemetacin Non-steroidal anti-inflammatory drug BANNED Acenocoumarol Anticoagulant CONTROLLED Acepromazine Sedative BANNED Acetanilid Analgesic/antipyretic CONTROLLED Acetazolamide Carbonic Anhydrase Inhibitor BANNED Acetohexamide Pancreatic stimulant CONTROLLED Acetominophen (Paracetamol) Analgesic BANNED Acetophenazine Antipsychotic BANNED Acetophenetidin (Phenacetin) Analgesic BANNED Acetylmorphine Narcotic BANNED Adinazolam Anxiolytic BANNED Adiphenine Antispasmodic BANNED Adrafinil Stimulant 1 December 2020, Lausanne, Switzerland 2021 Equine Prohibited Substances List . Prohibited Substances include any other substance with a similar chemical structure or similar biological effect(s).
    [Show full text]
  • Synthesis and Biological Activities of Local Anesthetics Cite This: RSC Adv.,2019,9, 41173 Shiyang Zhou,A Gangliang Huang *B and Guangying Chen*A
    RSC Advances View Article Online REVIEW View Journal | View Issue Synthesis and biological activities of local anesthetics Cite this: RSC Adv.,2019,9, 41173 Shiyang Zhou,a Gangliang Huang *b and Guangying Chen*a Local anesthetics are mainly used in stomatology, ophthalmology, gynecology and surgery to temporarily relieve pain. Local anesthetics act on nerve endings or around nerve trunks, and are combined with specific sodium ion (Na+) channel sites on the nerve membrane. They can affect the membrane potential by reducing Na+ passage through sodium ion channels, thus blocking the generation and conduction of Received 8th November 2019 nerve impulses, reversibly blocking the generation and conduction of sensory nerve impulses. Local Accepted 27th November 2019 anesthetics are used for convenience in local surgical operations and treatments. Herein, we mainly DOI: 10.1039/c9ra09287k review the research progress on local anesthetics and discuss the important aspects of design, synthesis rsc.li/rsc-advances and biological activity of various new compounds. – Creative Commons Attribution-NonCommercial 3.0 Unported Licence. 1. Introduction which is mainly used before surgery.8 11 In contrast, local anesthetics act on nerve endings or around nerve trunks, Anesthetics are a type of drug that act on the nervous system, reversibly blocking the generation and conduction of sensory causing it to be inhibited and resulting in the loss of the sense nerve impulses, and temporarily eliminating local sensation of pain.1–4 According to the different scopes of action of drugs, (mainly pain sensation) under the condition of consciousness. the department of anesthetics is divided into general anes- Moreover, it is convenient for local surgical operations and – thetics and local anesthetics.5–7 General anesthetics act on the treatments.12 14 Local anesthetics are mainly used in stomatol- central nervous system, causing it to be reversibly inhibited, ogy, ophthalmology, gynecology and surgery to relieve pain thereby resulting in a loss of consciousness and sensation.
    [Show full text]
  • Rational Design, Synthesis, and In-Silico Evaluation of Homologous Local Anesthetic Compounds As TASK-1 Channel Blockers †
    Proceeding Paper Rational Design, Synthesis, and In-Silico Evaluation of Homologous Local Anesthetic Compounds as TASK-1 Channel Blockers † Lorena Camargo-Ayala 1, Luis Prent-Peñaloza 2, Mauricio Bedoya 3, Margarita Gutiérrez 2,* and Wendy González 3,4,* 1 Doctorate in Sciences Mention in Research and Development of Bioactive Products, Institute of Chemistry of Natural Resources, Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), University of Talca, Casilla 747, Talca 3460000, Chile; [email protected] 2 Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), Institute of Chemistry of Natural Resources, University of Talca, Casilla 747, Talca 3460000, Chile; [email protected] 3 Center for Bioinformatics and Molecular Simulations (CBSM), Universidad de Talca, Casilla 747, Talca 3460000, Chile; [email protected] 4 Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD). Universidad de Talca, Casilla 747, Talca 3460000, Chile * Correspondence: [email protected] (M.G.); [email protected] (W.G.) † Presented at the 24th International Electronic Conference on Synthetic Organic Chemistry, 15 November–15 December 2020; Available online: https://ecsoc-24.sciforum.net/. Abstract: Advances in different technological and scientific fields have led to the development of tools that allow the design of drugs in a rational way, using defined therapeutic targets, and through Citation: Camargo-Ayala, L.; simulations that offer a molecular view of the ligand–receptor interactions, giving precise infor-
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,056,044 B2 MO Et Al
    USOO9056.04.4B2 (12) United States Patent (10) Patent No.: US 9,056,044 B2 MO et al. (45) Date of Patent: *Jun. 16, 2015 (54) ALPROSTADIL AND LIDOCAINE Y10S 514/947 (2013.01); A61K 47/10 TREATMENT OF PREMATURE (2013.01); A61 K47/14 (2013.01); A61K47/26 EUACULATION (2013.01); A61 K3I/20 (2013.01); A61 K 3 1/4453 (2013.01) (71) Applicant: NexMed Holdings, Inc., San Diego, CA (58) Field of Classification Search (US) CPC ............ A61 K31/5575; A61 K31/445; A61 K (72) Inventors: Y. Joseph Mo, Princeton, NJ (US); 9/0014; A61 K9/0034; A61 K31/167 Minggi Lu, Lawrenceville, NJ (US); USPC .......... 514/573, 330, 331, 947, 626; 424/400, Qin Wang, Plainsboro, NJ (US); James 424/434:562/503 L. Yeager, Lake Forest, IL (US) See application file for complete search history. (73) Assignee: NEXMED HOLDINGS, INC., San (56) References Cited Diego, CA (US) U.S. PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this 4.954,487 A 9/1990 Cooper et al. patent is extended or adjusted under 35 5,151,448 A 9, 1992 Crenshaw et al. U.S.C. 154(b) by 0 days. 5,234,957 A 8, 1993 Mantelle 5,314.915 A 5/1994 Rencher This patent is Subject to a terminal dis 5,332,576 A 7, 1994 Mantelle claimer. 5,654,337 A 8, 1997 Roentsch et al. 5,708,031 A 1, 1998 Scott 5,922,341 A 7/1999 Smith et al. (21) Appl. No.: 14/463,966 5,942.545 A 8, 1999 Samour et al.
    [Show full text]
  • Comparison of Effects of Selected Local Anesthetics on Sodium and Potassium Channels in Mammalian Neuron
    Gen. Physiol. Biophys. (1988), 7,177—189 177 Comparison of Effects of Selected Local Anesthetics on Sodium and Potassium Channels in Mammalian Neuron S. ŠTOLC Institute of Experimental Pharmacology, Centre of Physiological Sciences, Slovak Academy of Sciences, 842 16 Bratislava, Czechoslovakia Abstract. Effects of procaine, trimecaine, and a new carbanilate local anesthetic, carbizocaine, on early sodium inward current and fast and slow components of potassium outward current in the membrane of the rat dorsal root ganglion neuron were studied using the internal dialysis and potential clamp techniques. All the currents studied were depressed in the presence of the drugs tested. However, for inhibition of the inward current concentrations lower by ap­ proximately one to more than two orders were sufficient compared to those required for similar inhibition of the outward currents. Carbizocaine was the most effective, procaine the least effective drug. Almost identical ratios of the negative logarithms of mean effective concentrations for blocking the inward and the outward current respectively, were found for each of the drugs tested. None of the drugs could be characterized as a specific blocker of sodium or potassium channels. It is concluded that the mechanisms of action of these three local anesthetics in all the three types of ion channels studied in the neuronal membrane are very similar regardless of both the type of the chemical bond in the intermediary chain of the molecules (ester, anilide, carbanilate) and the structure of the aromatic moiety, or the absolute potency of the drug. Key words: Local anesthetics — Sodium ion channels — Potassium ion channels — Potential clamp technique — Isolated neuron dialysis Introduction It is generally accepted that the block of conduction of action potential in excitable cells elicited by common local anesthetics is mainly due to inhibition of activation of sodium channels (Shanes 1958; Strichartz 1976; Covino and The paper is dedicated to Prof.
    [Show full text]