Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 65, Issue 3, Pages 2522-2531Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c01967
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- Skaggs Institute for Chemical Biology
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This study implements immunopharmacotherapy to combat benzimidazole-derived new psychoactive substance (NPS) opioids. By producing antibodies with high titers and nanomolar affinity, psychoactive and physiological responses to NPS opioids can be mitigated. Additionally, the pharmacokinetics of these drugs and the challenges faced by traditional pharmaceutical opioid antagonists are discussed.
New psychoactive substance (NPS) opioids have proliferated within the international drug market. While synthetic opioids are traditionally composed of fentanyl analogues, benzimidazole-derived isotonitazene and its derivatives are the current NPS opioids of concern. Hence, in this study, we implement immunopharmacotherapy wherein antibodies are produced with high titers and nanomolar affinity to multiple benzimidazole-derived NPS opioids (BNO). Notably, these antibodies blunt psychoactive and physiological repercussions from BNO exposure, which was observed through antinociception, whole-body plethysmography, and blood-brain biodistribution studies. Moreover, we detail previously unreported pharmacokinetics of these drugs, which explains the struggle of traditional pharmaceutical opioid antagonists against BNO substances. These findings provide further insight into the in vivo effects of BNO drugs and the development of effective broad-spectrum therapeutics against NPS opioids.
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