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


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    "doi": "10.1021/acschemneuro.5b00107", 
    "description": "<p>Synthetic cannabinoid (SC) designer drugs featuring bioisosteric fluorine substitution are identified by forensic chemists and toxicologists with increasing frequency. Although terminal fluorination of <em>N</em>-pentyl indole SCs is sometimes known to improve cannabinoid type 1 (CB<sub>1</sub>) receptor binding affinity, little is known of the effects of fluorination on functional activity of SCs. This study explores the <em>in vitro</em> 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 CB<sub>1</sub> and CB<sub>2</sub> receptors using a FLIPR membrane potential assay. All compounds demonstrated agonist activity at CB<sub>1</sub> (EC<sub>50</sub> = 2.8&ndash;1959 nM) and CB<sub>2</sub> (EC<sub>50</sub> = 6.5&ndash;206 nM) receptors, with the fluorinated analogues generally showing increased CB<sub>1</sub> receptor potency (&sim;2&ndash;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 <em>in vivo</em> were evaluated in rats using biotelemetry. All SCs dose-dependently induced hypothermia and reduced heart rate at doses of 0.3&ndash;10 mg/kg. There was no consistent trend for increased potency of fluorinated SCs over the corresponding des-fluoro SCs <em>in vivo</em>. 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).</p>", 
    "license": {
      "id": "CC-BY-4.0"
    }, 
    "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.", 
    "journal": {
      "volume": "6", 
      "year": "2015", 
      "issue": "8", 
      "pages": "1445-58", 
      "title": "ACS Chem Neurosci"
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        "title": "Imaging of Neuroinflammation in Neurodegenerative Diseases", 
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        "program": "FP7", 
        "funder": {
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    "keywords": [
      " Cannabinoid", 
      "THC", 
      "JWH-018", 
      "AM-2201", 
      "XLR-11", 
      "PB-22"
    ], 
    "publication_date": "2015-05-08", 
    "creators": [
      {
        "name": "Banister, Samuel D"
      }, 
      {
        "name": "Stuart, Jordyn"
      }, 
      {
        "name": "Kevin, Richard C"
      }, 
      {
        "name": "Edington, Amelia"
      }, 
      {
        "name": "Longworth, Mitchell"
      }, 
      {
        "name": "Wilkinson, Shane M"
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      {
        "name": "Beinat, Corinne"
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      {
        "name": "Buchanan, Alexandra S"
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      {
        "name": "Hibbs, David E"
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      {
        "name": "Glass, Michelle"
      }, 
      {
        "name": "Connor, Mark"
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      {
        "name": "McGregor, Iain S"
      }, 
      {
        "name": "Kassiou, Michael"
      }
    ], 
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      "type": "publication", 
      "title": "Journal article"
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