Abstract:
Introduction: Atopic dermatitis (AD) is one of the most prevalent intractable chronic itch diseases worldwide. In recent years, new molecular-targeted drugs have emerged, but side effects and economic challenges remain. Therefore, since it is important for AD patients to have a wider range of treatment options, it is important to explore new therapeutic agents. Gabapentinoids, gabapentin and pregabalin, have been shown to be effective for the clinical treatment of several chronic itch. Recently, mirogabalin (MGB) was developed as a novel gabapentinoid. MGB is a drug for neuropathic pain and has a margin of safety between its side effects and the analgesic effect for animal experiments. Herein, we showed that MGB exhibited an antipruritic effect in a mouse model of AD using NC/Nga mice. Methods and results: The oral administration of MGB (10 mg/kg) inhibited spontaneous scratching behavior in AD mice and its effect was dose dependently. Then, when MGB (10 mg/kg) was orally administrated to healthy mice, it did not affect motor function, including locomotor activity, wheel activity, and coordinated movement. Moreover, gabapentin (100 mg/kg) and pregabalin (30 mg/kg), inhibited spontaneous scratching behavior in AD mice and decreased motor function in healthy mice. Furthermore, intracisternal injection of MGB (10 μg/site) significantly suppressed spontaneous scratching behavior in AD mice. Discussion: In summary, our results suggest that MGB exerts an antipruritic effect via the spinal dorsal horn using NC/Nga mice. We hope that MGB is a candidate for a novel therapeutic agent for AD with relatively few side effects.
摘要:
简介:特应性皮炎(AD)是世界上最常见的顽固性慢性瘙痒疾病之一。近年来,新的分子靶向药物已经出现,但副作用和经济挑战依然存在。因此,因为AD患者有更广泛的治疗选择是很重要的,探索新的治疗药物很重要。加巴喷丁,加巴喷丁和普瑞巴林,已被证明对几种慢性瘙痒的临床治疗有效。最近,米罗加巴巴林(MGB)是一种新型的类加巴喷丁。MGB是用于神经性疼痛的药物,并且在其副作用和用于动物实验的镇痛作用之间具有安全边际。在这里,我们发现MGB在使用NC/Nga小鼠的AD小鼠模型中表现出止痒作用。方法和结果:口服MGB(10mg/kg)可抑制AD小鼠的自发抓挠行为,其作用呈剂量依赖性。然后,当MGB(10mg/kg)口服给健康小鼠时,它没有影响运动功能,包括运动活动,车轮活动,协调运动。此外,加巴喷丁(100mg/kg)和普瑞巴林(30mg/kg),抑制AD小鼠的自发抓挠行为,并降低健康小鼠的运动功能。此外,脑池内注射MGB(10μg/位点)可显着抑制AD小鼠的自发抓挠行为。讨论:总之,我们的结果表明,使用NC/Nga小鼠,MGB通过脊髓背角发挥止痒作用。我们希望MGB是一种新型AD治疗剂的候选药物,副作用相对较少。