This Article Full Text (PDF) All Versions of this Article: 0269881108091551v1 23/6/633    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Zuurman, L Articles by van Gerven, J. Search for Related Content PubMed PubMed Citation Articles by Zuurman, L Articles by van Gerven, J. Social Bookmarking                         What's this?

Pharmacodynamic and pharmacokinetic effects of the intravenously administered CB1 receptor agonist Org 28611 in healthy male volunteers

Centre for Human Drug Research, Leiden, The Netherlands linekezuurman{at}gmail.com

PCCM Passier

NV Organon, Oss, The Netherlands

ML de Kam

Centre for Human Drug Research, Leiden, The Netherlands

HJ Kleijn

NV Organon, Oss, The Netherlands

AF Cohen

Centre for Human Drug Research, Leiden, The Netherlands

JMA van Gerven

Centre for Human Drug Research, Leiden, The Netherlands

Abstract

CB1/CB2 agonists are reported to have sedative, amnestic, analgesic and anti-emetic properties, which would make them ideal drugs for outpatient treatments under conscious sedation. The main objective of this in human study was to assess the sedative properties of Org 28611, a potent water-soluble CB1 agonist. Single ascending doses were administered during a slow 25 min infusion and after a 1 min bolus administration to healthy male volunteers. In addition, the pharmacokinetics, amnestic properties, postural stability, electro-encephalography, behavioural and cardiovascular effects were studied. Midazolam 0.1 mg/kg was used as a positive control. The pharmacokinetic parameters were proportional to dose. No effects were observed after intravenous administration of doses up to Org 28611 1 µg/kg. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 28611 3-10 µg/kg, the observed sedation was considerably less than after midazolam. Org 28611 is, therefore, not suitable for providing sedation for outpatient surgical procedures and doses above the maximum tolerated dose of 3 µg/kg (either administered as a slow infusion or a bolus dose) can cause untoward psychotropic effects.

Key Words: cannabinoid • CB1 receptor agonist • Org 28611 • intravenous • sedation • healthy volunteers • human • pharmacodynamics • pharmacokinetics

This version was published on August 1, 2009

Journal of Psychopharmacology, Vol. 23, No. 6, 633-644 (2009)
DOI: 10.1177/0269881108091551


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?