Journal article Open Access

Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135.

Banister, Samuel D; Stuart, Jordyn; Kevin, Richard C; Edington, Amelia; Longworth, Mitchell; Wilkinson, Shane M; Beinat, Corinne; Buchanan, Alexandra S; Hibbs, David E; Glass, Michelle; Connor, Mark; McGregor, Iain S; Kassiou, Michael


Dublin Core Export

<?xml version='1.0' encoding='utf-8'?>
<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Banister, Samuel D</dc:creator>
  <dc:creator>Stuart, Jordyn</dc:creator>
  <dc:creator>Kevin, Richard C</dc:creator>
  <dc:creator>Edington, Amelia</dc:creator>
  <dc:creator>Longworth, Mitchell</dc:creator>
  <dc:creator>Wilkinson, Shane M</dc:creator>
  <dc:creator>Beinat, Corinne</dc:creator>
  <dc:creator>Buchanan, Alexandra S</dc:creator>
  <dc:creator>Hibbs, David E</dc:creator>
  <dc:creator>Glass, Michelle</dc:creator>
  <dc:creator>Connor, Mark</dc:creator>
  <dc:creator>McGregor, Iain S</dc:creator>
  <dc:creator>Kassiou, Michael</dc:creator>
  <dc:date>2015-05-08</dc:date>
  <dc:description>Synthetic cannabinoid (SC) designer drugs featuring bioisosteric fluorine substitution are identified by forensic chemists and toxicologists with increasing frequency. Although terminal fluorination of N-pentyl indole SCs is sometimes known to improve cannabinoid type 1 (CB1) receptor binding affinity, little is known of the effects of fluorination on functional activity of SCs. This study explores the in vitro functional activities of SC designer drugs JWH-018, UR-144, PB-22, and APICA, and their respective terminally fluorinated analogues AM-2201, XLR-11, 5F-PB-22, and STS-135 at human CB1 and CB2 receptors using a FLIPR membrane potential assay. All compounds demonstrated agonist activity at CB1 (EC50 = 2.8–1959 nM) and CB2 (EC50 = 6.5–206 nM) receptors, with the fluorinated analogues generally showing increased CB1 receptor potency (∼2–5 times). Additionally, the cannabimimetic activities and relative potencies of JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135 in vivo were evaluated in rats using biotelemetry. All SCs dose-dependently induced hypothermia and reduced heart rate at doses of 0.3–10 mg/kg. There was no consistent trend for increased potency of fluorinated SCs over the corresponding des-fluoro SCs in vivo. Based on magnitude and duration of hypothermia, the SCs were ranked for potency (PB-22 &gt; 5F-PB-22 = JWH-018 &gt; AM-2201 &gt; APICA = STS-135 = XLR-11 &gt; UR-144).</dc:description>
  <dc:identifier>https://zenodo.org/record/47750</dc:identifier>
  <dc:identifier>10.1021/acschemneuro.5b00107</dc:identifier>
  <dc:identifier>oai:zenodo.org:47750</dc:identifier>
  <dc:relation>info:eu-repo/grantAgreement/EC/FP7/278850/</dc:relation>
  <dc:relation>url:https://zenodo.org/communities/inmind</dc:relation>
  <dc:relation>url:https://zenodo.org/communities/ecfunded</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>https://creativecommons.org/licenses/by/4.0/legalcode</dc:rights>
  <dc:source>ACS Chem Neurosci 6(8) 1445-58 (2015)</dc:source>
  <dc:subject> Cannabinoid</dc:subject>
  <dc:subject>THC</dc:subject>
  <dc:subject>JWH-018</dc:subject>
  <dc:subject>AM-2201</dc:subject>
  <dc:subject>XLR-11</dc:subject>
  <dc:subject>PB-22</dc:subject>
  <dc:title>Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135.</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>
1,043
753
views
downloads
Views 1,043
Downloads 753
Data volume 5.0 GB
Unique views 1,009
Unique downloads 698

Share

Cite as