Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
The Ken and Ruth Davee Department of Neurology, Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Drug Des Devel Ther. 2022 Apr 21;16:1143-1157. doi: 10.2147/DDDT.S354779. eCollection 2022.
Gastric ulcer induced by NSAIDs is the major medical concern and researchers are utilizing several approaches to combat this medical issue. In the current study, we investigated the efficacy of thiadiazinethione derivative (2,2'(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid, as new less ulcerogenic compound.
2,2'(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid was evaluated using standard animal models including hot plate, writhing test and formalin induced nociceptive models. Anti-inflammatory activity was assessed via carrageenan-induced paw oedema model. Involvement of opioidergic nociceptive mechanism was confirmed via naloxone administration in hot plat assay. The gastro-ulcerogenic potential of test and standard compounds were evaluated via NSAID-induced pyloric ligation model followed by standard histopathological and biochemical analysis.
In acetic acid-induced writhing test, our compound significantly reduced abdominal constrictions at the tested doses of 15 ( < 0.05), 30 ( < 0.01) and 45 mg kg ( < 0.001) as compared to control ( < 0.001). In hot plate test, after 30 min of administration, our test compound showed significant anti-nociceptive potential ( < 0.05 at 15 and 30 mg kg and < 0.01 at 45 mg kg) and tramadol ( ˂ 0.001) at 30 mg kg dose. After 60 min tramadol (30 kg) and test sample (30, 45 mg kg) exhibited significant anti-nociceptive activity < 0.001. In Formalin-induced nociceptive response, a significant decline ( ˂ 0.001) was observed for aspirin and test compound during acute and chronic phases. Decline in the anti-nociceptive potential of tramadol and test sample via administration of naloxone indicate the involvement of opioidergic mechanism. Our compound exhibited significant anti-inflammatory activity in second phase of carrageenan induced paw oedema model. Histological and biochemical parameters exhibited less ulcerogenic potential as compared to aspirin.
Our findings suggests that our test compound has desirable anti-nociceptive and anti-inflammatory potentials with less propensity to cause gastric ulcer.
非甾体抗炎药（NSAIDs）引起的胃溃疡是主要的医学关注点，研究人员正在利用多种方法来解决这个医学问题。在本研究中，我们研究了噻二嗪酮衍生物（2,2'（2-硫代-1,3,5-噻二嗪-3,5-二基）二乙酸）作为一种新的低致溃疡化合物的疗效。
使用包括热板、扭体试验和福尔马林诱导的伤害性模型在内的标准动物模型来评估 2,2'（2-硫代-1,3,5-噻二嗪-3,5-二基）二乙酸。通过角叉菜胶诱导的爪肿胀模型评估抗炎活性。通过在热板试验中给予纳洛酮来确认阿片类伤害性机制的参与。通过 NSAID 诱导的幽门结扎模型评估测试和标准化合物的胃溃疡形成潜力，然后进行标准组织病理学和生化分析。
在醋酸诱导的扭体试验中，与对照组相比（ < 0.001），我们的化合物在测试剂量为 15（ < 0.05）、30（ < 0.01）和 45 mg kg 时显著减少了腹部收缩（ < 0.001）。在热板试验中，给药 30 min 后，我们的测试化合物表现出显著的镇痛潜力（在 15 和 30 mg kg 时为 < 0.05，在 45 mg kg 时为 < 0.01），而曲马多（ < 0.001）在 30 mg kg 剂量下。60 min 后，曲马多（30 kg）和测试样品（30、45 mg kg）在急性和慢性阶段均表现出显著的镇痛活性（ < 0.001）。在福尔马林诱导的伤害性反应中，阿司匹林和测试化合物在急性和慢性阶段均显著下降（ < 0.001）。纳洛酮给药后曲马多和测试样品的镇痛潜力下降表明涉及阿片类机制。我们的化合物在卡拉胶诱导的爪肿胀模型的第二阶段表现出显著的抗炎活性。组织学和生化参数显示出比阿司匹林更低的致溃疡潜力。
我们的研究结果表明，我们的测试化合物具有理想的镇痛和抗炎潜力，且不易引起胃溃疡。
