(12) Patent Application Publication (10) Pub. No.: US 2003/0206942 A1 Kulkarni Et Al

Total Page:16

File Type:pdf, Size:1020Kb

(12) Patent Application Publication (10) Pub. No.: US 2003/0206942 A1 Kulkarni Et Al US 20030206942A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0206942 A1 Kulkarni et al. (43) Pub. Date: Nov. 6, 2003 (54) FAST DISSOLVING ORALLY CONSUMABLE Related U.S. Application Data FILMS CONTAINING AN ANTITUSSIVE AND A MUCOSA COATINGAGENT (63) Continuation-in-part of application No. 09/395,104, filed on Sep. 14, 1999, now Pat. No. 6,596,298. (76)76 Inventors: Neema Kulkarni, Randolph, NJ (US); (60) 25,Provisional 1998. application No. 60/101,798, filed on Sep. Lori D. Kumar, Skillman, NJ (US); Albert Sorg, Columbia, NJ (US) Publication Classification Correspondence Address: (51) Int. Cl." ....................... A61K 38/38; A61K 31/715; Barry H. Jacobsen A61K 9/70 Warner-Lambert Company (52) U.S. Cl. ............................... 424/443; 514/21; 514/54 Legal Division 201 Tabor Road (57) ABSTRACT Morris Plains, NJ 07950 (US) A consumable film adapted to adhere to and dissolve in the (21) Appl. No.: 10/423,735 oral cavity of a consumer comprising at least one water Soluble polymer, at least one antituSSive agent and a mucosa (22) Filed: Apr. 25, 2003 coating effective amount of a mucosa-coating agent. US 2003/0206942 A1 Nov. 6, 2003 EAST DISSOLVING ORALLY CONSUMABLE DETAILED DESCRIPTION FILMS CONTAINING AN ANTITUSSIVE AND A 0006 The present invention is directed to a physiological MUCOSA COATINGAGENT acceptable consumable film that is adapted to dissolve in the mouth of a consumer and adhere to the mucosa of the oral FIELD OF THE INVENTION cavity. Consumable films with mucosa coating agents are 0001. The present invention is related generally to fast particularly well-Suited for delivering an antituSSive agent to dissolving orally consumable films, more particularly to the consumer and are useful for treating or alleviating the films containing an antituSSive agent in combination with a Symptoms and/or irritations associated with Sore throats mucosa-coating agent in amounts Sufficient to impart and/or coughing. extended throat-coating and mucosa adherence properties. 0007. In one aspect of the present invention, there is provided a consumable film adapted to adhere to and dis BACKGROUND OF RELATED Solve in the mouth of a consumer including at least one TECHNOLOGIES water Soluble polymer, at least one antituSSive agent and a mucosa-coating effective amount of a mucosa-coating agent. 0002 Personal care products can be formulated in a The mucosa-coating agent is capable of forming a coating variety of dosage forms, including tablets, capsules, loz that adheres to the mucosa of the mouth and throat whereby enges or strips of edible thin film compositions. Edible thin the antituSSive agent is effectively retained in contact with film compositions applied to the oral cavity can be designed the affected areas of the mouth and throat for a period time to deliver therapeutic agents to the oral mucosa. One Such after the consumable film has dissolved. example is LISTERINE POCKETPAKSTM brand oral care 0008. The consumable film may include one or more of strip products made by Pfizer Inc. of New York are success the following ingredients, including, but not limited to, ful examples of an edible film compositions effective in water, antimicrobial agents, additional film forming agents delivering therapeutic agents particularly antimicrobial or water Soluble polymers, plasticizing agents, flavorings, agents in the form of a combination of essential oils. Sulfur precipitating agents, Saliva Stimulating agents, cool ing agents, Surfactants, Stabilizing agents, emulsifying 0.003 Conventional rapidly dissolving orally consumable agents, thickening agents, binding agents, coloring agents, films absorb water and may become Viscous and Sticky over triglycerides, polyethylene oxides, propylene glycols, time when applied to the moist Surface of the mucosa of the Sweeteners, fragrances, preservatives and the like, as oral cavity. Retention of the film may be insufficient to described in co-pending application U.S. patent application obtain the desired effect because the film rapidly disinte Ser. No. 09/395,104, by Leung et al., filed Sep. 14, 1999, grates within a relatively short time. Sometimes is it desir which is incorporated herein by reference. able to have improved covering and adherence to the 0009. In another embodiment of the present invention, mucosa Surface. Thus, there is a need in the art to develop the consumable film comprises a single layer including at consumable thin films, having good adhesion and retention least one water Soluble polymer, at least one antituSSive to the mucosa of the oral cavity for providing an effective agent and a mucosa-coating effective amount of pectin. delivery and retention System for antituSSive and mucosa coating agents. 0010. The term “consumable” as used herein is intended to encompass Substances including edible compounds, which upon administration to a consumer, is adequately SUMMARY tolerated without causing undue adverse effects or discom 0004. The present invention is generally directed to a fort to the consumer. consumable film, which is particularly well adapted to 0011 Unless specified otherwise, the term “% by weight” rapidly dissolve in the mouth of a consumer. In one particu as used is based on the total weight of the final product (i.e., lar aspect of the present invention, there is provided a the consumable film) as opposed to the formulation used to consumable film adapted to adhere to and dissolve in the produce the product, and thus denotes the percent of the total mouth of a consumer comprising at least one water Soluble dry weight contributed by the subject ingredient. This theo polymer, at least one antituSSive agent and a mucosa-coating retical value can differ from the experimental value, because effective amount of a mucosa-coating agent. In one embodi in practice, the consumable film typically retains Some of the ment, the mucosa-coating agent is pectin. water and/or other Substances Such as alcohol (e.g. ethanol) 0005 Another aspect of the present invention is directed that may be used in preparing the final product. to a method of preparing a Supple, non-Self-adhering film 0012. In one embodiment, the consumable film of the especially Suitable for oral delivery of at least one antituS present invention is shaped and sized for administration to Sive agent. The method comprises preparing an aqueous the oral cavity. The mucosa-coating agent is capable of phase comprising a mucosa-coating effective amount of a imparting throat Soothing and throat coating properties to the mucosa-coating agent, preparing a film-forming mixture consumable film as the film dissolves in the consumer's including at least one water Soluble polymer; combining the mouth. The dissolved film adheres to the Surface of the aqueous phase and the film forming mixture to form a mouth, typically the roof of the mouth or the tongue, and hydrated polymer gel; casting the hydrated polymer gel on coats and adheres to the mucosa of the throat, thus providing a Substrate to form a cast gel, and drying the cast gel to form maximum retention thereon for an extended period of time. the consumable film, wherein the at least one antituSSive AS a result, the consumable film of the present invention agent is added to the aqueous phase, the hydrated polymer affords an effective delivery and retention system for thera gel or both. peutic agents to localized areas within the oral cavity for US 2003/0206942 A1 Nov. 6, 2003 which treatment with the therapeutic agent is desired. Suit the consumable film is from about 0.01% to about 80% by able mucosa-coating agents include pectin, gelatin, and the weight based on the total weight of the consumable film, like, and combinations thereof. In one embodiment, the preferably from about 2.5% to about 40% by weight, and mucosa-coating agent may be present in amounts ranging more preferably from about 5% to about 30% by weight. from about 0.01% to about 5% by weight, in another embodiment, from about 0.1% to about 2% by weight, and 0017. A film can measure from about 1" by about 1.25" yet another embodiment, from about 0.1% to about 1.0% by (2.54 cmx3.18 cm) and weigh from about 60 mg to about weight of the consumable film. 190 mg. 0013 Suitable antitussive agent include alloclamide, 0018. Additional therapeutic agents that are effective for amicibone, benproperine, benzonatate, bibenzonium bro treating conditions other than coughing may be added to mide, bromoform, butamirate, butetamate, caramiphen various embodiments of the present invention, Such as an ethanedisulfonate, caramiphen edisylate, carbetapentane, antihistamine, Symphathomimetic pharmaceutically active chlophedianol, clobutinol, cloperastine, codeine, codeine agent (nasal decongestant, bronchodilator), analgesic, anti methyl bromide, codeine N-oxide, codeine phosphate, inflammatory, cough expectorant and the like, as described codeine Sulfate, cyclexanone, dextromethorphan, dibunate in co-pending application U.S. patent application Ser. No. Sodium, dihydrocodeine, dihydrocodeinone enol acetate, 09/395,104, by Leung et al., filed Sep. 14, 1999, which is dimenorfan, dimethoxanate, W.W-diphenyl-2-pip incorporated herein by reference. Other examples of Such eridinepropanol, dropropizine, drotebanol, eprazinone, ethyl additional therapeutic agents are well known in the art. dibunate, ethylmorphine, fominoben, guaiapate, hydroc 0019 Useful antihistamines include cetirizine, diphenhy odone, isoaminile, levopropoxyphene, morclofone, narce dramine, loratadine, desloratadine, feXofenadine, mon ine, normethadone, noScapine, OXeladin, oxolamine, phol telukast Sodium, and the like. codine, picoperine, pipaZethate, piperidione, prenoXcdiazine hydrochloride, racemethorphan, taZiprinone hydrochloride, 0020 Examples of doses for specific pharmaceutically tipepidine, Zipeprol, and the like and pharmaceutically active agents that can be delivered per one Strip of rapidly acceptable Salts thereof, and combinations thereof. The dissolving oral film are reviewed in Table A. antituSSive agents as utilized in the present invention may be in the free form or in any non-toxic pharmaceutically TABLE A acceptable form wherein their therapeutic activity is Pharmaceutically Active Agent Dose retained.
Recommended publications
  • Therapeutic Class Brand Name P a Status Generic
    P A Therapeutic Class Brand Name Status Generic Name Strength Form Absorbable Sulfonamides AZULFIDINE SULFASALAZINE 250MG/5ML ORAL SUSP Absorbable Sulfonamides AZULFIDINE SULFASALAZINE 500MG TABLET Absorbable Sulfonamides AZULFIDINE SULFASALAZINE 500MG TABLET DR Absorbable Sulfonamides BACTRIM DS SULFAMETHOXAZOLE/TRIMETHO 800-160MG TABLET Absorbable Sulfonamides GANTRISIN SULFISOXAZOLE 500MG TABLET Absorbable Sulfonamides GANTRISIN SULFISOXAZOLE ACETYL 500MG/5ML ORAL SUSP Absorbable Sulfonamides GANTRISIN SULFISOXAZOLE ACETYL 500MG/5ML SYRUP Absorbable Sulfonamides SEPTRA SULFAMETHOXAZOLE/TRIMETHO 200-40MG/5 ORAL SUSP Absorbable Sulfonamides SEPTRA SULFAMETHOXAZOLE/TRIMETHO 400-80MG TABLET Absorbable Sulfonamides SULFADIAZINE SULFADIAZINE 500MG TABLET ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 10-20MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 2.5-10MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 5-10MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 5-20MG CAPSULE P A Therapeutic Class Brand Name Status Generic Name Strength Form ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 5-40MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 10-40MG CAPSULE Acne Agents, Systemic ACCUTANE ISOTRETINOIN 10MG CAPSULE Acne Agents, Systemic ACCUTANE ISOTRETINOIN 20MG CAPSULE Acne Agents, Systemic ACCUTANE
    [Show full text]
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • Prohibited Substances List
    Prohibited Substances List This is the Equine Prohibited Substances List that was voted in at the FEI General Assembly in November 2009 alongside the new Equine Anti-Doping and Controlled Medication Regulations(EADCMR). Neither the List nor the EADCM Regulations are in current usage. Both come into effect on 1 January 2010. The current list of FEI prohibited substances remains in effect until 31 December 2009 and can be found at Annex II Vet Regs (11th edition) Changes in this List : Shaded row means that either removed or allowed at certain limits only SUBSTANCE ACTIVITY Banned Substances 1 Acebutolol Beta blocker 2 Acefylline Bronchodilator 3 Acemetacin NSAID 4 Acenocoumarol Anticoagulant 5 Acetanilid Analgesic/anti-pyretic 6 Acetohexamide Pancreatic stimulant 7 Acetominophen (Paracetamol) Analgesic/anti-pyretic 8 Acetophenazine Antipsychotic 9 Acetylmorphine Narcotic 10 Adinazolam Anxiolytic 11 Adiphenine Anti-spasmodic 12 Adrafinil Stimulant 13 Adrenaline Stimulant 14 Adrenochrome Haemostatic 15 Alclofenac NSAID 16 Alcuronium Muscle relaxant 17 Aldosterone Hormone 18 Alfentanil Narcotic 19 Allopurinol Xanthine oxidase inhibitor (anti-hyperuricaemia) 20 Almotriptan 5 HT agonist (anti-migraine) 21 Alphadolone acetate Neurosteriod 22 Alphaprodine Opiod analgesic 23 Alpidem Anxiolytic 24 Alprazolam Anxiolytic 25 Alprenolol Beta blocker 26 Althesin IV anaesthetic 27 Althiazide Diuretic 28 Altrenogest (in males and gelidngs) Oestrus suppression 29 Alverine Antispasmodic 30 Amantadine Dopaminergic 31 Ambenonium Cholinesterase inhibition 32 Ambucetamide Antispasmodic 33 Amethocaine Local anaesthetic 34 Amfepramone Stimulant 35 Amfetaminil Stimulant 36 Amidephrine Vasoconstrictor 37 Amiloride Diuretic 1 Prohibited Substances List This is the Equine Prohibited Substances List that was voted in at the FEI General Assembly in November 2009 alongside the new Equine Anti-Doping and Controlled Medication Regulations(EADCMR).
    [Show full text]
  • Daniel Bovet
    D ANIEL B OVET The relationships between isosterism and competitive phenomena in the field of drug therapy of the autonomic nervous system and that of the neuromuscular transmission Nobel Lecture, December 11, 1957 Putting to good use the vast possibilities which organic synthesis offers, a number of workers have directed their efforts towards applying it to thera- peutics, and have sought to establish the bases of a science of pharmaceutical chemistry, or, more exactly perhaps, the bases of a science of chemical pharmacology worthy of this name. If such an ambitious programme has not yet been fully realized, we are at least justified in recognizing, in the work which has now been in progress for fifty years, the appearance of a few guiding principles whose value has not ceased to assert itself. This is particularly true, for example, in the case of ideas in isosterism and com- petition. The origin of many drugs must be looked for in substances of a biological nature, and in particular in the alkaloids. The elucidation of their structure has been a starting-off point for chemists to synthesize similar compounds. Cocaine, atropine, and morphia are particularly good examples in this respect, since substances which are made like them have shown, clinically, local anaesthetic, antispasmodic, and marked analgesic properties, respective- ly. In each of these cases the physiological properties of the new compound seem to be similar to the compound to which it is structurally related. This has been verified in many other fields, but it is nevertheless evident that in certain cases, molecules which are chemically closely related have very dif- ferent and even antagonistic properties.
    [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) Patent Application Publication (10) Pub. No.: US 2005/0281875A1 Srinivasan Et Al
    US 2005O281.875A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0281875A1 Srinivasan et al. (43) Pub. Date: Dec. 22, 2005 (54) PROMETHAZINE CONTAINING DOSAGE Related U.S. Application Data FORM (63) Continuation-in-part of application No. 10/736,902, (75) Inventors: Viswanathan Srinivasan, The filed on Dec. 17, 2003. Woodlands, TX (US); Ralph Brown, Southlake, TX (US); David Brown, Publication Classification Colleyville, TX (US); Himanshu Patel, North Richland Hills, TX (US) (51) Int. Cl." ........................ A61K 3.1/5415; A61K 9/24 (52) U.S. Cl. ......................................... 424/472; 514/225.8 Correspondence Address: GREENBLUM & BERNSTEIN, P.L.C. ABSTRACT 1950 ROLAND CLARKE PLACE (57) RESTON, VA 20191 (US) A pharmaceutical dosage form which comprises promethaz (73) Assignee: Sovereign Pharmaceuticals, Ltd., Fort ine and/or a pharmaceutically acceptable Salt thereof. The Worth, TX dosage form is capable of providing a promethazine plasma concentration within a therapeutic range for at least about 24 (21) Appl. No.: 11/102,725 hours per Single dose. This Abstract is neither intended to define the invention disclosed in this specification nor (22) Filed: Apr. 11, 2005 intended to limit the Scope of the invention in any way. US 2005/0281875 A1 Dec. 22, 2005 PROMETHAZINE CONTAINING DOSAGE FORM or in combination with another drug, for example, pseu doephedrine, is indicated, could obtain relief by ingesting CROSS-REFERENCE TO RELATED only one dosage per 24 hour period. Not only would this APPLICATIONS convenient dosage form increase compliance with ambula tory patients, it would also simplify dosage for patients in 0001. The present application is a continuation-in-part of institutional care, Such as nursing homes and hospitals, U.S.
    [Show full text]
  • POISONS LIST APPENDIX Amoebicides: Carbarsone
    POISONS LIST APPENDIX Amoebicides: Carbarsone Clioquinol and other halogenated hydroxyquinoline compounds Dehydroemetine; its salts Diloxanide; its compounds Dimetridazole Emetine Ipronidazole Metronidazole Pentamidine; its salts Ronidazole Anaesthetics: Alphadolone acetate Alphaxolone Desflurane Disoprofol Enflurane Ethyl ether Etomidate; its salts Halothane Isoflurane Ketamine; its salts Local anaesthetics, the following: their salts; their homologues and analogues; their molecular compounds Amino-alcohols esterified with benzoic acid, phenylacetic acid, phenylpropionic acid, cinnamic acid or the derivatives of these acids; their salts Benzocaine Bupivacaine Butyl aminobenzoate Cinchocaine Diperodon Etidocaine Levobupivacaine Lignocaine Mepivacaine Orthocaine Oxethazaine Phenacaine Phenodianisyl Prilocaine Ropivacaine Phencyclidine; its salts Propanidid Sevoflurane Tiletamine; its salts Tribromoethanol Analeptics and Central Stimulants: Amiphenazole; its salts Amphetamine (DD) Bemegride Cathine Cathinone (DD) Dimethoxybromoamphetamine (DOB) (DD) 2, 5-Dimethoxyamphetamine (DMA) (DD) 2, 5-Dimethoxy-4-ethylamphetamine (DOET) (DD) Ethamivan N-Ethylamphetamine; its salts N-Ethyl MDA (DD) N-Hydroxy MDA (DD) Etryptamine (DD) Fencamfamine Fenetylline Lefetamine or SPA or (-)-1-dimethylamino-1, 2-diphenylethane Leptazol Lobelia, alkaloids of Meclofenoxate; its salts Methamphetamine (DD) Methcathinone (DD) 5-Methoxy-3, 4-methylenedioxyamphetamine (MMDA) (DD) Methylenedioxyamphetamine (MDA) (DD) 3, 4-Methylenedioxymetamphetamine (MDMA) (DD) Methylphenidate;
    [Show full text]
  • Codeine and Its Alternates for Pain and Cough Relief
    Codeine and its Alternates for Pain and Cough Relief 3. The Antitussive Action of Codeine-Mechanism, Methodology and Evaluation This report-the third of a series on codeine and its alternates for pain and cough relief-presents a detailed review of the physiology and pathophysiology of cough, the methods for the experimental and clinical measurement of the antitussive action of drugs, possible mechanisms of action of antitussive agents, and includes a compilation of experi­ mental results and clinical experience with codeine as an antitussive. CONTENTS INTRODUCTION 127 PHARMACOLOGICAL COMPONENTS OF THE ANTITUSSIVE EFFECT • MECHANISM AND SIGNIFICANCE OF COUGH 128 136 ANTITUSSIVE ACTION OF CODEINE 143 METHODS FOR THE STUDY OF ANTITUSSIVE RESUME 153 ACTION 130 REFERENCES 154 INTRODUCTION of codeine has increased greatly in recent years (see Part 4) but the popularity of codeine continues and Codeine was first used as a therapeutic antitussive its annual consumption remains at a high level, paral­ agent soon after its separation as an alkaloidal entity leling the high frequency of need for relief of cough (Martin, 1834) and some of the earliest accounts of as a symptom, especially chronic cough. Bickerman dosage and of the circumstances of its use are sum­ (1960) estimated, not so long ago, that 13% of the marized by K.rueger, Eddy & Sumwalt (1943). population of the United States of America was more Codeine has indeed dominated the picture with than 65 years old and that there were not less than respect to the symptomatic management of cough, 1 300 000 chronic coughers. Watt (1958) estimated with only minor variations, and this situation has that in the United Kingdom of Great Britain and been influenced little by the intro,duction of sub­ Northern Ireland 10% of all prescriptions were for stances claimed to be superior in effectiveness and cough relief.
    [Show full text]
  • Pharmacological Therapies Against Soman-Induced Seizures in Rats 30 Min
    (Review) Choice of approaches in developing novel medical countermeasures for nerve agent poisoning Trond Myhrer, Pål Aas Norwegian Defence Research Establishment (FFI), Protection and Societal Security Division, P. O. Box 25, NO-2027 Kjeller, Norway Running title: Nerve agent poisoning and countermeasures Correspondence: Pål Aas Norwegian Defence Research Establishment (FFI) Protection and Societal Security Division P O Box 25 NO-2027 Kjeller, Norway Phone: +47 63 80 78 43 Fax: +47 63 80 75 09 E-mail: [email protected] Dette er en postprint-versjon / This is a postprint version. DOI til publisert versjon / DOI to published version: 10.1016/j.neuro.2014.04.011 2 Abstract During the establishment of a research branch, all relevant matters encountered will be of interest to study. After having acquired a body of basal knowledge, it becomes possible to derive ideas or hypotheses for further elaboration of information. The purpose of the present study was to show that therapies for nerve agent poisoning based on specific neuropharmacological approaches can have greater probability for being successful than treatment regimens based on fragmental research or serendipitous discoveries. By following the guidelines for research in experimental epilepsy, neuronal target areas for nerve agents have been identified through lesion studies, and critical receptors for pharmacological treatment have been specified through microinfusion studies of rats. Subsequent experimentations have shown that the results achieved from microinfusion studies are transferable to systemic administration. It is demonstrated that a treatment regimen developed through the novel approach is more efficacious than regimens derived from conventional research on countermeasures. A therapy consisting of HI-6, levetiracetam, and procyclidine that has been worked out along the new lines, exerts powerful anticonvulsant capacity and appears to have universal utility as a stand-alone therapy against soman intoxication in rats.
    [Show full text]
  • Cutaneous Analgesia and Systemic Toxicity of Carbetapentane And
    Manuscript 1 Cutaneous analgesia and systemic toxicity of carbetapentane and caramiphen in rats Ching-Hsia Hunga , Ph.D., Chin-Chen Chub, M.D., Ph.D., Yu-Chung Chenc, M.S., Kuo-Sheng Liud, Ph.D., Yu-Wen Chenb,e,*, Ph.D., Jhi-Joung Wangb, M.D., Ph.D. a Institute & Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan; b Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; c Division of Physical Therapy, Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan; d Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy & Science, Tainan, Taiwan; e Department of Physical Therapy, China Medical University, Taichung, Taiwan 1. Ching-Hsia Hung, Ph.D. Title: Associate Professor Affiliation: National Cheng Kung University Email: [email protected] Role: This author helped design the study, conduct the study, and analyze the data Conflicts: Ching-Hsia Hung reported no conflicts of interest Attestation: Ching-Hsia Hung has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files 2. Chin-Chen Chu, M.D., Ph.D. Title: Assistant Professor Affiliation: Chi-Mei Medical Center Email: [email protected] Role: This author helped conduct the study and analyze the data Conflicts: Chin-Chen Chu reported no conflicts of interest Attestation: Chin-Chen Chu has seen the study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for 2 archiving the study files 3. Yu-Chung Chen, M.S.
    [Show full text]
  • Routinely Tested Analytes
    FORENSIC TOXICOLOGY LABORATORY OFFICE OF CHIEF MEDICAL EXAMINER CITY OF NEW YORK ROUTINELY TESTED ANALYTES Listed below are drugs that are routinely included in comprehensive toxicology testing and subsequently confirmed and quantitated. (Applicable analytical methodologies are in parentheses.) VOLATILES AND GASES Ethanol (HS/GC) Acetone (HS/GC)Uncontrolled Copy 2-propanol (HS/GC) Methanol (HS/GC) Carbon monoxide (SP, CT) INCLUDED WITH POSITIVE ELISA FOR: 1. Opiates: Morphine, codeine, 6-MAM, hydrocodone, hydromorphone, oxycodone, oxymorphone (LC/MS) 2. Benzoylecgonine: cocaine, benzoylecgonine (LC/MS) 3. Barbiturates: pentobarbital, phenobarbital, secobarbital, amobarbital, butabarbital, butalbital, phenytoin, carbamazepine (HPLC) 4. Benzodiazepines: diazepam, nordiazepam, oxazepam, temazepam, alprazolam, alphahydroxyalprazolam triazolam, clonazepam, 7-aminoclonazepam, lorazepam, 7-amino flunitrazepam (GC/MS) 5. Amphetamines: amphetamine, methamphetamine, MDA, MDMA, MDEA, ephedrine, pseudoephedrine, phenylpropanlolamine, paramethoxyamphetamine. (GC/MS) 6. Oxycodone: see drugs in Opiates above plus acetaminophen (LC/MS, HPLC) 7. Methadone: methadone (and any other drugs indentified from the same extraction. 8. Cannabinoids (as needed): unconfirmed screening test BASED ON HISTORY: Vitreous chemistry: glucose, lithium Carbon monoxide Page 1 of 5 In addition to the above, the following drugs are routinely included in comprehensive toxicology testing with subsequent confirmation and quantitation. (Applicable analytical methodologies are in
    [Show full text]
  • Multiple Pharmacological Actions of Centrally Acting Antitussives — Do They Target G Protein-Coupled Inwardly Rectifying K+ (GIRK) Channels?
    J Pharmacol Sci 120, 146 – 151 (2012) Journal of Pharmacological Sciences © The Japanese Pharmacological Society Current Perspective Multiple Pharmacological Actions of Centrally Acting Antitussives — Do They Target G Protein-Coupled Inwardly Rectifying K+ (GIRK) Channels? Kazuo Takahama1,* 1Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 0e-honmachi, Kumamoto 862-0973, Japan Received May 28, 2012; Accepted August 20, 2012 Abstract. Antitussive drugs have been used for decades and their modes of action are well elu- cidated. However, recent studies on the mechanism of their antitussive action seem to be opening a new way for discovery or development of novel drugs for intractable brain diseases including psychiatric disorders. Antitussives inhibit the currents caused by activation of G protein-coupled inwardly rectifying K+ (GIRK) channels in neurons. In our own studies carried out so far, we found that antitussives possessing an inhibitory action on GIRK channels, similar to the effects of an enriched environment, ameliorate symptoms of intractable brain diseases in various animal models. In this review, the multiple pharmacological actions of the antitussives are described, and their mechanisms are discussed addressing GIRK channels as a possible molecular target. Keywords: G protein-coupled inwardly rectifying K+ (GIRK) channel, centrally acting antitussive, antidepressant-like action, enriched environment, dopamine 1. Introduction tors (GPCRs) in the brain
    [Show full text]