An integrated cardiovascular and neurobehavioural functional assessment in the conscious telemetered cynomolgus monkey
Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. The purpose of this study was to validate, in the monkey, a model that incorporates the neurobehavioural assessment into the Safety Pharmacology cardiovas...
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| Veröffentlicht in: | Journal of pharmacological and toxicological methods 2010-09, Vol.62 (2), p.95-106 |
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| creator | Moscardo, Elena McPhie, Gordon Fasdelli, Nicola Dorigatti, Roberto Meecham, Ken |
| description | Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. The purpose of this study was to validate, in the monkey, a model that incorporates the neurobehavioural assessment into the Safety Pharmacology cardiovascular study, allowing for an integrated evaluation of these two physiological systems.
Conscious male cynomolgus (Macaca fascicularis) monkeys (n=4) were given single oral doses of vehicle, d-amphetamine (0.5, 1 and 2mg/kg) or diazepam (0.5, 1 and 2.5mg/kg) in a dose-escalation study design. Blood pressure, heart rate, electrocardiogram (ECG), body temperature, locomotor activity and behaviour (by video) were monitored continuously for 24h post-dose. Animals underwent a standardised neurobehavioural test battery which allowed the direct examination of 31 signs, including behavioural responses and neurological examinations, conducted the day before dose, at maximal plasma concentration time (Tmax), and 24h post-dose. The study was carried out in a first phase with telemetric cardiovascular recording only, and a second phase with telemetric cardiovascular recording and neurobehavioural observations. Results from the second phase of the study were used to evaluate the influence of the direct neurobehavioural examination on the telemetrically acquired cardiovascular parameters.
The expected cardiovascular and neurobehavioural changes, based on the pharmacological properties of the compounds tested, were accurately detected. In the second phase of the study the direct neurobehavioural examination caused fluctuations of the telemetric cardiovascular parameters for no more than 20min from the end of the procedure and this did not alter or jeopardise the analysis and interpretation of the cardiovascular parameters.
These results confirm the validity of this combined model capable of providing in the cynomolgus monkey a reliable and reproducible neurobehavioural and cardiovascular assessment of candidate drugs during the course of safety pharmacology evaluations. |
| doi_str_mv | 10.1016/j.vascn.2010.06.006 |
| format | Article |
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Conscious male cynomolgus (Macaca fascicularis) monkeys (n=4) were given single oral doses of vehicle, d-amphetamine (0.5, 1 and 2mg/kg) or diazepam (0.5, 1 and 2.5mg/kg) in a dose-escalation study design. Blood pressure, heart rate, electrocardiogram (ECG), body temperature, locomotor activity and behaviour (by video) were monitored continuously for 24h post-dose. Animals underwent a standardised neurobehavioural test battery which allowed the direct examination of 31 signs, including behavioural responses and neurological examinations, conducted the day before dose, at maximal plasma concentration time (Tmax), and 24h post-dose. The study was carried out in a first phase with telemetric cardiovascular recording only, and a second phase with telemetric cardiovascular recording and neurobehavioural observations. Results from the second phase of the study were used to evaluate the influence of the direct neurobehavioural examination on the telemetrically acquired cardiovascular parameters.
The expected cardiovascular and neurobehavioural changes, based on the pharmacological properties of the compounds tested, were accurately detected. In the second phase of the study the direct neurobehavioural examination caused fluctuations of the telemetric cardiovascular parameters for no more than 20min from the end of the procedure and this did not alter or jeopardise the analysis and interpretation of the cardiovascular parameters.
These results confirm the validity of this combined model capable of providing in the cynomolgus monkey a reliable and reproducible neurobehavioural and cardiovascular assessment of candidate drugs during the course of safety pharmacology evaluations.</description><identifier>ISSN: 1056-8719</identifier><identifier>EISSN: 1873-488X</identifier><identifier>DOI: 10.1016/j.vascn.2010.06.006</identifier><identifier>PMID: 20601019</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amphetamine ; Animals ; Anti-Anxiety Agents - administration & dosage ; Anti-Anxiety Agents - pharmacology ; Behavior, Animal - drug effects ; Blood Pressure - drug effects ; Body Temperature - drug effects ; Cardiovascular ; Cardiovascular Physiological Phenomena - drug effects ; Cardiovascular System - drug effects ; Central Nervous System Stimulants - administration & dosage ; Central Nervous System Stimulants - pharmacology ; Cynomolgus ; Dextroamphetamine - administration & dosage ; Dextroamphetamine - pharmacology ; Diazepam - administration & dosage ; Diazepam - pharmacology ; Dose-Response Relationship, Drug ; Electrocardiography - drug effects ; Heart Rate - drug effects ; Macaca fascicularis ; Male ; Methods ; Monkey ; Motor Activity - drug effects ; Neurobehavioural observation battery ; Numerical score ; Telemetry ; Video images</subject><ispartof>Journal of pharmacological and toxicological methods, 2010-09, Vol.62 (2), p.95-106</ispartof><rights>2010 Elsevier Inc.</rights><rights>2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-6c2c35fa9f728e602746eede4358be9cdd560a8d3a5889233cbcfeea5d3e7bf93</citedby><cites>FETCH-LOGICAL-c390t-6c2c35fa9f728e602746eede4358be9cdd560a8d3a5889233cbcfeea5d3e7bf93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.vascn.2010.06.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20601019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moscardo, Elena</creatorcontrib><creatorcontrib>McPhie, Gordon</creatorcontrib><creatorcontrib>Fasdelli, Nicola</creatorcontrib><creatorcontrib>Dorigatti, Roberto</creatorcontrib><creatorcontrib>Meecham, Ken</creatorcontrib><title>An integrated cardiovascular and neurobehavioural functional assessment in the conscious telemetered cynomolgus monkey</title><title>Journal of pharmacological and toxicological methods</title><addtitle>J Pharmacol Toxicol Methods</addtitle><description>Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. The purpose of this study was to validate, in the monkey, a model that incorporates the neurobehavioural assessment into the Safety Pharmacology cardiovascular study, allowing for an integrated evaluation of these two physiological systems.
Conscious male cynomolgus (Macaca fascicularis) monkeys (n=4) were given single oral doses of vehicle, d-amphetamine (0.5, 1 and 2mg/kg) or diazepam (0.5, 1 and 2.5mg/kg) in a dose-escalation study design. Blood pressure, heart rate, electrocardiogram (ECG), body temperature, locomotor activity and behaviour (by video) were monitored continuously for 24h post-dose. Animals underwent a standardised neurobehavioural test battery which allowed the direct examination of 31 signs, including behavioural responses and neurological examinations, conducted the day before dose, at maximal plasma concentration time (Tmax), and 24h post-dose. The study was carried out in a first phase with telemetric cardiovascular recording only, and a second phase with telemetric cardiovascular recording and neurobehavioural observations. Results from the second phase of the study were used to evaluate the influence of the direct neurobehavioural examination on the telemetrically acquired cardiovascular parameters.
The expected cardiovascular and neurobehavioural changes, based on the pharmacological properties of the compounds tested, were accurately detected. In the second phase of the study the direct neurobehavioural examination caused fluctuations of the telemetric cardiovascular parameters for no more than 20min from the end of the procedure and this did not alter or jeopardise the analysis and interpretation of the cardiovascular parameters.
These results confirm the validity of this combined model capable of providing in the cynomolgus monkey a reliable and reproducible neurobehavioural and cardiovascular assessment of candidate drugs during the course of safety pharmacology evaluations.</description><subject>Amphetamine</subject><subject>Animals</subject><subject>Anti-Anxiety Agents - administration & dosage</subject><subject>Anti-Anxiety Agents - pharmacology</subject><subject>Behavior, Animal - drug effects</subject><subject>Blood Pressure - drug effects</subject><subject>Body Temperature - drug effects</subject><subject>Cardiovascular</subject><subject>Cardiovascular Physiological Phenomena - drug effects</subject><subject>Cardiovascular System - drug effects</subject><subject>Central Nervous System Stimulants - administration & dosage</subject><subject>Central Nervous System Stimulants - pharmacology</subject><subject>Cynomolgus</subject><subject>Dextroamphetamine - administration & dosage</subject><subject>Dextroamphetamine - pharmacology</subject><subject>Diazepam - administration & dosage</subject><subject>Diazepam - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrocardiography - drug effects</subject><subject>Heart Rate - drug effects</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Methods</subject><subject>Monkey</subject><subject>Motor Activity - drug effects</subject><subject>Neurobehavioural observation battery</subject><subject>Numerical score</subject><subject>Telemetry</subject><subject>Video images</subject><issn>1056-8719</issn><issn>1873-488X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0Eol_8AiSUG6cs4zjxx4FDVRWoVKmXIvVmOfak9ZLYxXZW2n-Ply0c4TSj0fO-M5qXkPcUNhQo_7Td7Ey2YdNBnQDfAPBX5JRKwdpeyofXtYeBt1JQdULOct4CAFO0f0tOOuBVRNUp2V2GxoeCj8kUdI01yfl48F1nkxoTXBNwTXHEJ7PzcU1mbqY12OJjqK3JGXNeMJRq0pQnbGwM2VYwNwVnXLBgOtjuQ1zi_FjHSww_cH9B3kxmzvjupZ6T71-u76--tbd3X2-uLm9byxSUltvOsmEyahKdRA6d6Dmiw54NckRlnRs4GOmYGaRUHWN2tBOiGRxDMU6KnZOPR9_nFH-umItefLY4zyZgPVJLKjgIpcR_STH0QOUgoJLsSNoUc0446efkF5P2moI-JKO3-ncy-pCMBq5rMlX14cV_HRd0fzV_oqjA5yOA9R87j0nXR2Kw6HxCW7SL_p8LfgERx6SV</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>Moscardo, Elena</creator><creator>McPhie, Gordon</creator><creator>Fasdelli, Nicola</creator><creator>Dorigatti, Roberto</creator><creator>Meecham, Ken</creator><general>Elsevier Inc</general><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>7X8</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20100901</creationdate><title>An integrated cardiovascular and neurobehavioural functional assessment in the conscious telemetered cynomolgus monkey</title><author>Moscardo, Elena ; McPhie, Gordon ; Fasdelli, Nicola ; Dorigatti, Roberto ; Meecham, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-6c2c35fa9f728e602746eede4358be9cdd560a8d3a5889233cbcfeea5d3e7bf93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amphetamine</topic><topic>Animals</topic><topic>Anti-Anxiety Agents - administration & dosage</topic><topic>Anti-Anxiety Agents - pharmacology</topic><topic>Behavior, Animal - drug effects</topic><topic>Blood Pressure - drug effects</topic><topic>Body Temperature - drug effects</topic><topic>Cardiovascular</topic><topic>Cardiovascular Physiological Phenomena - drug effects</topic><topic>Cardiovascular System - drug effects</topic><topic>Central Nervous System Stimulants - administration & dosage</topic><topic>Central Nervous System Stimulants - pharmacology</topic><topic>Cynomolgus</topic><topic>Dextroamphetamine - administration & dosage</topic><topic>Dextroamphetamine - pharmacology</topic><topic>Diazepam - administration & dosage</topic><topic>Diazepam - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrocardiography - drug effects</topic><topic>Heart Rate - drug effects</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Methods</topic><topic>Monkey</topic><topic>Motor Activity - drug effects</topic><topic>Neurobehavioural observation battery</topic><topic>Numerical score</topic><topic>Telemetry</topic><topic>Video images</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moscardo, Elena</creatorcontrib><creatorcontrib>McPhie, Gordon</creatorcontrib><creatorcontrib>Fasdelli, Nicola</creatorcontrib><creatorcontrib>Dorigatti, Roberto</creatorcontrib><creatorcontrib>Meecham, Ken</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Journal of pharmacological and toxicological methods</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moscardo, Elena</au><au>McPhie, Gordon</au><au>Fasdelli, Nicola</au><au>Dorigatti, Roberto</au><au>Meecham, Ken</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An integrated cardiovascular and neurobehavioural functional assessment in the conscious telemetered cynomolgus monkey</atitle><jtitle>Journal of pharmacological and toxicological methods</jtitle><addtitle>J Pharmacol Toxicol Methods</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>62</volume><issue>2</issue><spage>95</spage><epage>106</epage><pages>95-106</pages><issn>1056-8719</issn><eissn>1873-488X</eissn><abstract>Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. The purpose of this study was to validate, in the monkey, a model that incorporates the neurobehavioural assessment into the Safety Pharmacology cardiovascular study, allowing for an integrated evaluation of these two physiological systems.
Conscious male cynomolgus (Macaca fascicularis) monkeys (n=4) were given single oral doses of vehicle, d-amphetamine (0.5, 1 and 2mg/kg) or diazepam (0.5, 1 and 2.5mg/kg) in a dose-escalation study design. Blood pressure, heart rate, electrocardiogram (ECG), body temperature, locomotor activity and behaviour (by video) were monitored continuously for 24h post-dose. Animals underwent a standardised neurobehavioural test battery which allowed the direct examination of 31 signs, including behavioural responses and neurological examinations, conducted the day before dose, at maximal plasma concentration time (Tmax), and 24h post-dose. The study was carried out in a first phase with telemetric cardiovascular recording only, and a second phase with telemetric cardiovascular recording and neurobehavioural observations. Results from the second phase of the study were used to evaluate the influence of the direct neurobehavioural examination on the telemetrically acquired cardiovascular parameters.
The expected cardiovascular and neurobehavioural changes, based on the pharmacological properties of the compounds tested, were accurately detected. In the second phase of the study the direct neurobehavioural examination caused fluctuations of the telemetric cardiovascular parameters for no more than 20min from the end of the procedure and this did not alter or jeopardise the analysis and interpretation of the cardiovascular parameters.
These results confirm the validity of this combined model capable of providing in the cynomolgus monkey a reliable and reproducible neurobehavioural and cardiovascular assessment of candidate drugs during the course of safety pharmacology evaluations.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20601019</pmid><doi>10.1016/j.vascn.2010.06.006</doi><tpages>12</tpages></addata></record> |
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| ispartof | Journal of pharmacological and toxicological methods, 2010-09, Vol.62 (2), p.95-106 |
| issn | 1056-8719 1873-488X |
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| subjects | Amphetamine Animals Anti-Anxiety Agents - administration & dosage Anti-Anxiety Agents - pharmacology Behavior, Animal - drug effects Blood Pressure - drug effects Body Temperature - drug effects Cardiovascular Cardiovascular Physiological Phenomena - drug effects Cardiovascular System - drug effects Central Nervous System Stimulants - administration & dosage Central Nervous System Stimulants - pharmacology Cynomolgus Dextroamphetamine - administration & dosage Dextroamphetamine - pharmacology Diazepam - administration & dosage Diazepam - pharmacology Dose-Response Relationship, Drug Electrocardiography - drug effects Heart Rate - drug effects Macaca fascicularis Male Methods Monkey Motor Activity - drug effects Neurobehavioural observation battery Numerical score Telemetry Video images |
| title | An integrated cardiovascular and neurobehavioural functional assessment in the conscious telemetered cynomolgus monkey |
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