Physostigmine and Hyoscine Improves Protection Against the Lethal and Incapacitating Effects of Nerve Agent Poisoning in the Guinea-Pig
This study is drawn from a work programme aimed at developing improved medical counter measures for nerve agent poisoning. Guinea-pigs were administered pyridostigmine (5.1 μg/h) or physostigmine (4.7 μg/h) and hyoscine (1.94 μg/h) for 6 days via a subcutaneously implanted mini osmotic pump. Pyridos...
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| Veröffentlicht in: | Neurotoxicology (Park Forest South) 2002-09, Vol.23 (3), p.341-349 |
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| creator | Wetherell, Janet Hall, Tracey Passingham, Sarah |
| description | This study is drawn from a work programme aimed at developing improved medical counter measures for nerve agent poisoning. Guinea-pigs were administered pyridostigmine (5.1
μg/h) or physostigmine (4.7
μg/h) and hyoscine (1.94
μg/h) for 6 days via a subcutaneously implanted mini osmotic pump. Pyridostigmine inhibited red cell acetylcholinesterase (AChE) by 44.2±2.7% and plasma cholinesterase (ChE) by 29.9±1.8%. Physostigmine and hyoscine inhibited red cell AChE by 18.7±3.7% and plasma ChE by 44.1±3.1%. On day 6, animals were challenged with a lethal dose of tabun (GA; 125
μg/kg), sarin (GB; 51.2
μg/kg), soman (GD; 31.2
μg/kg), GF (50
μg/kg) or VX (11.25
μg/kg) administered by the subcutaneous route. Animals were closely observed for signs of poisoning. The time to the onset of signs of poisoning was similar for all the agents except for VX, which showed a delay compared to the other agents. Following pretreatment with either pyridostigmine or physostigmine and hyoscine most animals survived for 2–3
h following nerve agent administration. In contrast, only physostigmine and hyoscine prevented or reduced the duration of the signs of incapacitation and the temperature drop produced by all the agents. Pyridostigmine-pretreated animals showed little or no recovery from incapacitation prior to death. Physostigmine and hyoscine pretreatment provided statistically (
P |
| doi_str_mv | 10.1016/S0161-813X(02)00082-7 |
| format | Article |
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μg/h) or physostigmine (4.7
μg/h) and hyoscine (1.94
μg/h) for 6 days via a subcutaneously implanted mini osmotic pump. Pyridostigmine inhibited red cell acetylcholinesterase (AChE) by 44.2±2.7% and plasma cholinesterase (ChE) by 29.9±1.8%. Physostigmine and hyoscine inhibited red cell AChE by 18.7±3.7% and plasma ChE by 44.1±3.1%. On day 6, animals were challenged with a lethal dose of tabun (GA; 125
μg/kg), sarin (GB; 51.2
μg/kg), soman (GD; 31.2
μg/kg), GF (50
μg/kg) or VX (11.25
μg/kg) administered by the subcutaneous route. Animals were closely observed for signs of poisoning. The time to the onset of signs of poisoning was similar for all the agents except for VX, which showed a delay compared to the other agents. Following pretreatment with either pyridostigmine or physostigmine and hyoscine most animals survived for 2–3
h following nerve agent administration. In contrast, only physostigmine and hyoscine prevented or reduced the duration of the signs of incapacitation and the temperature drop produced by all the agents. Pyridostigmine-pretreated animals showed little or no recovery from incapacitation prior to death. Physostigmine and hyoscine pretreatment provided statistically (
P<0.05) better protection against GB, GD and VX lethality (24
h) than pyridostigmine pretreatment and better protection against GA and GF lethality.</description><identifier>ISSN: 0161-813X</identifier><identifier>EISSN: 1872-9711</identifier><identifier>DOI: 10.1016/S0161-813X(02)00082-7</identifier><identifier>PMID: 12387361</identifier><language>eng</language><publisher>Orlando, FL: Elsevier B.V</publisher><subject>Animals ; Antidotes - pharmacology ; Biological and medical sciences ; Body Temperature - drug effects ; Chemical and industrial products toxicology. Toxic occupational diseases ; Chemical Warfare Agents - toxicity ; Cholinesterase Inhibitors - pharmacology ; Cholinesterases - blood ; Drug Implants ; Guinea Pigs ; Incapacitation ; Lethality ; Male ; Medical sciences ; Muscarinic Antagonists - pharmacology ; Nerve agent ; Organothiophosphorus Compounds - administration & dosage ; Organothiophosphorus Compounds - toxicity ; Physostigmine - pharmacology ; Physostigmine and hyoscine ; Pyridostigmine ; Pyridostigmine Bromide - pharmacology ; Scopolamine Hydrobromide - pharmacology ; Toxicology ; Various organic compounds ; Weight Gain - drug effects</subject><ispartof>Neurotoxicology (Park Forest South), 2002-09, Vol.23 (3), p.341-349</ispartof><rights>2002</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-e6114ba94fa50dee5d47e57befc318e761894dbf1ff1de8b39010cfa28816613</citedby><cites>FETCH-LOGICAL-c422t-e6114ba94fa50dee5d47e57befc318e761894dbf1ff1de8b39010cfa28816613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0161-813X(02)00082-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13952549$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12387361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wetherell, Janet</creatorcontrib><creatorcontrib>Hall, Tracey</creatorcontrib><creatorcontrib>Passingham, Sarah</creatorcontrib><title>Physostigmine and Hyoscine Improves Protection Against the Lethal and Incapacitating Effects of Nerve Agent Poisoning in the Guinea-Pig</title><title>Neurotoxicology (Park Forest South)</title><addtitle>Neurotoxicology</addtitle><description>This study is drawn from a work programme aimed at developing improved medical counter measures for nerve agent poisoning. Guinea-pigs were administered pyridostigmine (5.1
μg/h) or physostigmine (4.7
μg/h) and hyoscine (1.94
μg/h) for 6 days via a subcutaneously implanted mini osmotic pump. Pyridostigmine inhibited red cell acetylcholinesterase (AChE) by 44.2±2.7% and plasma cholinesterase (ChE) by 29.9±1.8%. Physostigmine and hyoscine inhibited red cell AChE by 18.7±3.7% and plasma ChE by 44.1±3.1%. On day 6, animals were challenged with a lethal dose of tabun (GA; 125
μg/kg), sarin (GB; 51.2
μg/kg), soman (GD; 31.2
μg/kg), GF (50
μg/kg) or VX (11.25
μg/kg) administered by the subcutaneous route. Animals were closely observed for signs of poisoning. The time to the onset of signs of poisoning was similar for all the agents except for VX, which showed a delay compared to the other agents. Following pretreatment with either pyridostigmine or physostigmine and hyoscine most animals survived for 2–3
h following nerve agent administration. In contrast, only physostigmine and hyoscine prevented or reduced the duration of the signs of incapacitation and the temperature drop produced by all the agents. Pyridostigmine-pretreated animals showed little or no recovery from incapacitation prior to death. Physostigmine and hyoscine pretreatment provided statistically (
P<0.05) better protection against GB, GD and VX lethality (24
h) than pyridostigmine pretreatment and better protection against GA and GF lethality.</description><subject>Animals</subject><subject>Antidotes - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Body Temperature - drug effects</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Chemical Warfare Agents - toxicity</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cholinesterases - blood</subject><subject>Drug Implants</subject><subject>Guinea Pigs</subject><subject>Incapacitation</subject><subject>Lethality</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscarinic Antagonists - pharmacology</subject><subject>Nerve agent</subject><subject>Organothiophosphorus Compounds - administration & dosage</subject><subject>Organothiophosphorus Compounds - toxicity</subject><subject>Physostigmine - pharmacology</subject><subject>Physostigmine and hyoscine</subject><subject>Pyridostigmine</subject><subject>Pyridostigmine Bromide - pharmacology</subject><subject>Scopolamine Hydrobromide - pharmacology</subject><subject>Toxicology</subject><subject>Various organic compounds</subject><subject>Weight Gain - drug effects</subject><issn>0161-813X</issn><issn>1872-9711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOEzEQRS0EYsLAJ4C8ATGLBle_7F6NRqN5RIogErNgZ7nd5cSoYwfbiZQv4LdxJxGzZFNWSedWle8l5D2wL8Cg_fojFygEVD8_s_KKMSbKgr8gMxC8LDoO8JLM_iEX5E2MvxiDhrfda3IBZSV41cKM_FmuD9HHZFcb65AqN9DHg496auabbfB7jHQZfEKdrHf0ZqWsi4mmNdIFprUaj5q502qrtE0qWbeid8ZkPlJv6DcMe8wydIkuvY3eTYB1xwkPu7xHFUu7ekteGTVGfHd-L8nT_d3T7WOx-P4wv71ZFLouy1RgC1D3qquNatiA2Aw1x4b3aHQFAnkLoquH3oAxMKDoq44B00aVQkDbQnVJPp3G5p_93mFMcmOjxnFUDv0uShAtqzmbwOYE6uBjDGjkNtiNCgcJTE4ByGMAcnJXslIeA5A86z6cF-z6DQ7PqrPjGfh4BlTUajRBOW3jM1d1TdnUXeauTxxmN_YWg8yhoNM42JC9lYO3_znlLwjkpJM</recordid><startdate>20020901</startdate><enddate>20020901</enddate><creator>Wetherell, Janet</creator><creator>Hall, Tracey</creator><creator>Passingham, Sarah</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20020901</creationdate><title>Physostigmine and Hyoscine Improves Protection Against the Lethal and Incapacitating Effects of Nerve Agent Poisoning in the Guinea-Pig</title><author>Wetherell, Janet ; Hall, Tracey ; Passingham, Sarah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-e6114ba94fa50dee5d47e57befc318e761894dbf1ff1de8b39010cfa28816613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Antidotes - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Body Temperature - drug effects</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Chemical Warfare Agents - toxicity</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cholinesterases - blood</topic><topic>Drug Implants</topic><topic>Guinea Pigs</topic><topic>Incapacitation</topic><topic>Lethality</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscarinic Antagonists - pharmacology</topic><topic>Nerve agent</topic><topic>Organothiophosphorus Compounds - administration & dosage</topic><topic>Organothiophosphorus Compounds - toxicity</topic><topic>Physostigmine - pharmacology</topic><topic>Physostigmine and hyoscine</topic><topic>Pyridostigmine</topic><topic>Pyridostigmine Bromide - pharmacology</topic><topic>Scopolamine Hydrobromide - pharmacology</topic><topic>Toxicology</topic><topic>Various organic compounds</topic><topic>Weight Gain - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wetherell, Janet</creatorcontrib><creatorcontrib>Hall, Tracey</creatorcontrib><creatorcontrib>Passingham, Sarah</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neurotoxicology (Park Forest South)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wetherell, Janet</au><au>Hall, Tracey</au><au>Passingham, Sarah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physostigmine and Hyoscine Improves Protection Against the Lethal and Incapacitating Effects of Nerve Agent Poisoning in the Guinea-Pig</atitle><jtitle>Neurotoxicology (Park Forest South)</jtitle><addtitle>Neurotoxicology</addtitle><date>2002-09-01</date><risdate>2002</risdate><volume>23</volume><issue>3</issue><spage>341</spage><epage>349</epage><pages>341-349</pages><issn>0161-813X</issn><eissn>1872-9711</eissn><abstract>This study is drawn from a work programme aimed at developing improved medical counter measures for nerve agent poisoning. Guinea-pigs were administered pyridostigmine (5.1
μg/h) or physostigmine (4.7
μg/h) and hyoscine (1.94
μg/h) for 6 days via a subcutaneously implanted mini osmotic pump. Pyridostigmine inhibited red cell acetylcholinesterase (AChE) by 44.2±2.7% and plasma cholinesterase (ChE) by 29.9±1.8%. Physostigmine and hyoscine inhibited red cell AChE by 18.7±3.7% and plasma ChE by 44.1±3.1%. On day 6, animals were challenged with a lethal dose of tabun (GA; 125
μg/kg), sarin (GB; 51.2
μg/kg), soman (GD; 31.2
μg/kg), GF (50
μg/kg) or VX (11.25
μg/kg) administered by the subcutaneous route. Animals were closely observed for signs of poisoning. The time to the onset of signs of poisoning was similar for all the agents except for VX, which showed a delay compared to the other agents. Following pretreatment with either pyridostigmine or physostigmine and hyoscine most animals survived for 2–3
h following nerve agent administration. In contrast, only physostigmine and hyoscine prevented or reduced the duration of the signs of incapacitation and the temperature drop produced by all the agents. Pyridostigmine-pretreated animals showed little or no recovery from incapacitation prior to death. Physostigmine and hyoscine pretreatment provided statistically (
P<0.05) better protection against GB, GD and VX lethality (24
h) than pyridostigmine pretreatment and better protection against GA and GF lethality.</abstract><cop>Orlando, FL</cop><pub>Elsevier B.V</pub><pmid>12387361</pmid><doi>10.1016/S0161-813X(02)00082-7</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0161-813X |
| ispartof | Neurotoxicology (Park Forest South), 2002-09, Vol.23 (3), p.341-349 |
| issn | 0161-813X 1872-9711 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_18604701 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antidotes - pharmacology Biological and medical sciences Body Temperature - drug effects Chemical and industrial products toxicology. Toxic occupational diseases Chemical Warfare Agents - toxicity Cholinesterase Inhibitors - pharmacology Cholinesterases - blood Drug Implants Guinea Pigs Incapacitation Lethality Male Medical sciences Muscarinic Antagonists - pharmacology Nerve agent Organothiophosphorus Compounds - administration & dosage Organothiophosphorus Compounds - toxicity Physostigmine - pharmacology Physostigmine and hyoscine Pyridostigmine Pyridostigmine Bromide - pharmacology Scopolamine Hydrobromide - pharmacology Toxicology Various organic compounds Weight Gain - drug effects |
| title | Physostigmine and Hyoscine Improves Protection Against the Lethal and Incapacitating Effects of Nerve Agent Poisoning in the Guinea-Pig |
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