Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers
An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties o...
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| Veröffentlicht in: | Journal of psychopharmacology (Oxford) 2010-11, Vol.24 (11), p.1689-1696 |
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| creator | Zuurman, L Passier, P CCM de Kam, M L Kleijn, H J Cohen, A F van Gerven, J MA |
| description | An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures. |
| doi_str_mv | 10.1177/0269881109106913 |
| format | Article |
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CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.</description><identifier>ISSN: 0269-8811</identifier><identifier>EISSN: 1461-7285</identifier><identifier>DOI: 10.1177/0269881109106913</identifier><identifier>PMID: 19939872</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adult ; Ambulatory Surgical Procedures ; Analgesics ; Anxiety ; Biological and medical sciences ; Cannabinoid CB1 receptors ; Central nervous system ; Conscious Sedation ; Dose-Response Relationship, Drug ; Dronabinol - adverse effects ; Dronabinol - analogs & derivatives ; Dronabinol - blood ; Dronabinol - pharmacokinetics ; Dronabinol - pharmacology ; Hallucinations ; Humans ; Hypnotics and Sedatives - adverse effects ; Hypnotics and Sedatives - pharmacokinetics ; Hypnotics and Sedatives - pharmacology ; Infusions, Intravenous ; Injections, Intravenous ; Intravenous administration ; Male ; Medical sciences ; Midazolam ; Midazolam - pharmacokinetics ; Midazolam - pharmacology ; Neuropharmacology ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology. Drug treatments ; Posture ; Receptor, Cannabinoid, CB1 - agonists ; Receptor, Cannabinoid, CB1 - drug effects ; Young Adult</subject><ispartof>Journal of psychopharmacology (Oxford), 2010-11, Vol.24 (11), p.1689-1696</ispartof><rights>The Author(s) 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-853e97aa8f3b50a31ce004d8fef250c90bee2ea184e3ba21e2454aaa5296b0cb3</citedby><cites>FETCH-LOGICAL-c426t-853e97aa8f3b50a31ce004d8fef250c90bee2ea184e3ba21e2454aaa5296b0cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0269881109106913$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0269881109106913$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>315,781,785,21823,27928,27929,43625,43626</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24301674$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19939872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zuurman, L</creatorcontrib><creatorcontrib>Passier, P CCM</creatorcontrib><creatorcontrib>de Kam, M L</creatorcontrib><creatorcontrib>Kleijn, H J</creatorcontrib><creatorcontrib>Cohen, A F</creatorcontrib><creatorcontrib>van Gerven, J MA</creatorcontrib><title>Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers</title><title>Journal of psychopharmacology (Oxford)</title><addtitle>J Psychopharmacol</addtitle><description>An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.</description><subject>Adult</subject><subject>Ambulatory Surgical Procedures</subject><subject>Analgesics</subject><subject>Anxiety</subject><subject>Biological and medical sciences</subject><subject>Cannabinoid CB1 receptors</subject><subject>Central nervous system</subject><subject>Conscious Sedation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dronabinol - adverse effects</subject><subject>Dronabinol - analogs & derivatives</subject><subject>Dronabinol - blood</subject><subject>Dronabinol - pharmacokinetics</subject><subject>Dronabinol - pharmacology</subject><subject>Hallucinations</subject><subject>Humans</subject><subject>Hypnotics and Sedatives - adverse effects</subject><subject>Hypnotics and Sedatives - pharmacokinetics</subject><subject>Hypnotics and Sedatives - pharmacology</subject><subject>Infusions, Intravenous</subject><subject>Injections, Intravenous</subject><subject>Intravenous administration</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Midazolam</subject><subject>Midazolam - pharmacokinetics</subject><subject>Midazolam - pharmacology</subject><subject>Neuropharmacology</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Posture</subject><subject>Receptor, Cannabinoid, CB1 - agonists</subject><subject>Receptor, Cannabinoid, CB1 - drug effects</subject><subject>Young Adult</subject><issn>0269-8811</issn><issn>1461-7285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0d2L1DAQAPAgireevvskARGfembSNE0evcUvODgf9LlMs9Pdnm26Junh_veXZYvKwXFPgZnfTGYYxl6DuACo6w9CamsMgLAgtIXyCVuB0lDU0lRP2eqYLo75M_YixhshQCtdPWdnYG1pTS1X7M_3HYYR3bQ5eBx7x9Fv-H6J_eo9pRyjriOXIp86nnbEe58C3pKf5sjXl8ADOdqnKXDcTr6PiV-HLZfaSJMp3xEOaXfgIw7Eb6dh9okoxJfsWYdDpFfLe85-fv70Y_21uLr-8m398apwSupUmKokWyOarmwrgSU4EkJtTEedrISzoiWShGAUlS1KIKkqhYiVtLoVri3P2ftT332Yfs8UUzP20dEwoKe8QGMrVeVJpXxU1lrIUlsNWb69J2-mOfi8RgNWGtDGCpuVOCkXphgDdc0-9COGQwOiOZ6vuX--XPJmaTy3I23-FSz3yuDdAjA6HLqA3vXxr5OqzDeuVXbFyUXc0n_TPfTxHXbarro</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Zuurman, L</creator><creator>Passier, P CCM</creator><creator>de Kam, M L</creator><creator>Kleijn, H J</creator><creator>Cohen, A F</creator><creator>van Gerven, J MA</creator><general>SAGE Publications</general><general>Sage Publications</general><general>Sage Publications Ltd</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>7X8</scope></search><sort><creationdate>20101101</creationdate><title>Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers</title><author>Zuurman, L ; Passier, P CCM ; de Kam, M L ; Kleijn, H J ; Cohen, A F ; van Gerven, J MA</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-853e97aa8f3b50a31ce004d8fef250c90bee2ea184e3ba21e2454aaa5296b0cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Ambulatory Surgical Procedures</topic><topic>Analgesics</topic><topic>Anxiety</topic><topic>Biological and medical sciences</topic><topic>Cannabinoid CB1 receptors</topic><topic>Central nervous system</topic><topic>Conscious Sedation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dronabinol - adverse effects</topic><topic>Dronabinol - analogs & derivatives</topic><topic>Dronabinol - blood</topic><topic>Dronabinol - pharmacokinetics</topic><topic>Dronabinol - pharmacology</topic><topic>Hallucinations</topic><topic>Humans</topic><topic>Hypnotics and Sedatives - adverse effects</topic><topic>Hypnotics and Sedatives - pharmacokinetics</topic><topic>Hypnotics and Sedatives - pharmacology</topic><topic>Infusions, Intravenous</topic><topic>Injections, Intravenous</topic><topic>Intravenous administration</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Midazolam</topic><topic>Midazolam - pharmacokinetics</topic><topic>Midazolam - pharmacology</topic><topic>Neuropharmacology</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Posture</topic><topic>Receptor, Cannabinoid, CB1 - agonists</topic><topic>Receptor, Cannabinoid, CB1 - drug effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zuurman, L</creatorcontrib><creatorcontrib>Passier, P CCM</creatorcontrib><creatorcontrib>de Kam, M L</creatorcontrib><creatorcontrib>Kleijn, H J</creatorcontrib><creatorcontrib>Cohen, A F</creatorcontrib><creatorcontrib>van Gerven, J MA</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>MEDLINE - Academic</collection><jtitle>Journal of psychopharmacology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zuurman, L</au><au>Passier, P CCM</au><au>de Kam, M L</au><au>Kleijn, H J</au><au>Cohen, A F</au><au>van Gerven, J MA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers</atitle><jtitle>Journal of psychopharmacology (Oxford)</jtitle><addtitle>J Psychopharmacol</addtitle><date>2010-11-01</date><risdate>2010</risdate><volume>24</volume><issue>11</issue><spage>1689</spage><epage>1696</epage><pages>1689-1696</pages><issn>0269-8811</issn><eissn>1461-7285</eissn><abstract>An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). 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| subjects | Adult Ambulatory Surgical Procedures Analgesics Anxiety Biological and medical sciences Cannabinoid CB1 receptors Central nervous system Conscious Sedation Dose-Response Relationship, Drug Dronabinol - adverse effects Dronabinol - analogs & derivatives Dronabinol - blood Dronabinol - pharmacokinetics Dronabinol - pharmacology Hallucinations Humans Hypnotics and Sedatives - adverse effects Hypnotics and Sedatives - pharmacokinetics Hypnotics and Sedatives - pharmacology Infusions, Intravenous Injections, Intravenous Intravenous administration Male Medical sciences Midazolam Midazolam - pharmacokinetics Midazolam - pharmacology Neuropharmacology Pharmacodynamics Pharmacokinetics Pharmacology. Drug treatments Posture Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - drug effects Young Adult |
| title | Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers |
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