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The neuroprotective effect of a novel 1,4‐Dihydroquinazolin‐3(2H)‐yl benzamide derivative against chronic constriction injury‐induced neuropathic pain in rats

Neuropathic pain (NP) is a severe, chronic inflammatory condition affecting both the central and peripheral nervous systems and is resistant to standard treatment. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used to treat NP, but they are not the best option due to their limited penetration of the blood‐brain barrier and the gastrointestinal side effects associated with long‐term use. We recently reported a new series of benzamide derivatives that inhibit cyclooxygenase 2 (COX2) with comparable selectivity to celecoxib and tolerable side effects. Among these derivatives, 4‐chloro‐N‐(2‐(4‐chlorophenyl)‐1‐methyl‐4‐oxo‐1,4‐dihydroquinazolin‐3(2H)‐yl)benzamide (4b) demonstrated potent anti‐inflammatory and analgesic properties, as well as 32‐fold greater CNS accessibility than celecoxib. We aim to investigate the anti‐inflammatory and anti‐nociceptive effects of 4b against NP utilizing chronic constriction injury (CCI) model of neuropathy, elucidating the molecular mechanisms involved in its effect on both the peripheral (sciatic nerve) and central (brainstem) levels.