The endocannabinoid system mediates the enhanced analgesia and GI safety advantage of a newly developed NSAID derivative
Enhanced Analgesic Effects and GI Safety of A Novel Hydrogen Sulfide‐Releasing Anti‐Inflammatory Drug (ATB‐352): A Role for Endogenous Cannabinoids
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the preferable alternatives to opioids in management of post-operative pain because they are not addictive; however, their use is limited by the substantial risk of bleeding and ulcer, particularly in the gastrointestinal (GI) tract. In animal models, derivatives of NSAIDs that contain a hydrogen sulfide (H2S)‐releasing group have been shown to cause markedly less GI damage than the parent NSAIDs.
Ketoprofen is a very potent but also among the most GI-toxic NSAID. ATB-352 is a newly developed H2S-releasing derivative of ketoprofen. Scientists recently evaluated the pain-relieving efficacy and the toxicity of ATB-352 in comparison with ketoprofen using a mouse model of enhanced sensitivity to pain. They found that ATB-352 elicits less GI damage. Furthermore, the study also showed that ATB-352 is significantly more potent as an analgesic (pain-relieving substance) than ketoprofen. When the cannabinoid receptor type 1 (CB1) was blocked prior to administration, the analgesic effect of ATB-352 was compromised, but that of ketoprofen was not. This observation led researchers to believe that a major mechanism of ATB-352’s analgesic effects - but not ketoprofen’s - is mediated by the cannabinoid receptor type 1 (CB1).
Not only does this study demonstrate the various advantages of ATB‐352, a H2S‐releasing derivative of ketoprofen, for pain control in postoperative setting, it also provides further evidence of the the endogenous cannabinoid system’s important role in biological pathways regulating pain sensation.