This effective compound is potentially safer than current drugs in alleviating acute and chronic pains, making it a promising substitute for standard pain killers.
Headaches and muscular pains may seem harmless at first glance, but the root cause of these conditions – the various inflammatory processes inside our body – can cause devastating chronic inflammatory diseases like cancer, chronic respiratory diseases, diabetes, heart disorders, obesity, and stroke. Chronic inflammatory diseases are also one of the most significant causes of death worldwide. In the United States alone, the prevalence of diseases associated with chronic inflammation is expected to rise persistently in the next three decades.
At present, the mainstays of managing pain and inflammation of chronic course conditions are non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase-1 or -2 (also known as COX-1/COX-2), and have been proven to be highly effective in reducing pain and fighting inflammation. However, NSAIDs can also cause some serious adverse side effects leading to heart failure, kidney malfunction, and stomach ulceration among others. Gastrointestinal bleeding and erosions, in particular, are the most commonly reported adverse drug reactions among NSAIDs users. Cardiovascular complications were also found to be correlated with doses and potency of COX-2 inhibition.
To lessen pain without harming the body, scientists have been trying to develop safer non-steroidal anti-inflammatory and analgesic drugs. In their recent study, scientists led by Dr. Kikuko Amagase from Ritsumeikan University, Japan, and Professor Adnan A. Bekhit, from the University of Alexandria, Egypt, explored the therapeutic efficacy and side effects of a highly promising compound known as AD732 in rat models.
“In a previous study, we synthesised this compound AD732. In this study, we compared it with two standard pharmaceutical drugs—indomethacin, a prototype NSAID, and celecoxib, a COX-2 inhibitor,” explained Dr. Amagase. “We aimed to assess its efficacy and adverse effects while relieving both acute and chronic pains.”
Using rat models of paw oedema and granuloma, Amagase, Bekhit, and colleagues investigated the anti-inflammatory properties of AD732. The scientists also examined the analgesic properties of the drug in a rat model of hyperalgesia and with hot plate tests which involve placing a rat on a temperature-controlled heated plate and monitoring the animal’s responses for signs of pain. The results of their study were highly encouraging as AD732 was found to not only induce greater anti-inflammatory and analgesic effects compared to standard agents, but also caused less ulcerogenic effects and minimal harm to kidney function.
Despite these benefits, further in vitro analyses of the drug’s mechanisms of action revealed that it was a less potent inhibitor of COX-2 than celecoxib. However, this may suggest that the drug has lower cardiovascular toxicity since previous studies have shown that highly potent COX-2 inhibitors tend to cause significant cardiac damage. Rofecoxib, a selective COX-2 inhibitor, for instance, was found to greatly increase the risk of heart attacks and was subsequently withdrawn from the market in 2004. Moreover, although AD732 seems to be a less selective inhibitor of COX-2, the drug has proven to be therapeutically effective in preventing rat paw oedema.
“Our findings on AD732’s lower COX-2 inhibition could indicate that this is not the sole mechanism contributing to its anti-inflammatory actions,” said Dr. Bekhit regarding the discrepancy of results in different diseases.
Further in-depth research will be needed to exactly determine AD732’s precise mechanism of action, but these findings bring hope that we may soon be able to kill pain without harming the body.
“It may be concluded that compound AD732 appears to be a safer and more effective molecule with promising potential for the management of pain and inflammation, even in difficult diseases such as ulcerative colitis and Crohn’s disease,” said Dr. Amagase. [APBN]
Source: Bekhit et al. (2022). Investigation of the anti-inflammatory and analgesic activities of promising pyrazole derivative. European Journal of Pharmaceutical Sciences, 168, 106080.