Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent.
Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent.
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DOI：
10.1038/s41598-018-27395-0
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发表时间：
2018-06-12
影响因子：
4.6
通讯作者：
Mousa SA
中科院分区：
文献类型：
--
作者：
Ayoub BM;Mowaka S;Safar MM;Ashoush N;Arafa MG;Michel HE;Tadros MM;Elmazar MM;Mousa SA
药物重新定位是药物发现的革命性突破，通过扫描现有候选药物作为治疗切换或重新用于上市药物，为已经更安全的药物提供了突出的特权。在先前与DPP-4抑制相关的研究中，西格列汀、维达格列汀、萨格列普汀和利那格列汀显示出抗氧化和神经恢复作用。文献表明，格列普汀没有穿过血脑屏障(BBB)，而奥马利普汀是本研究中第一个成功跨越血脑屏障的格列普汀。LC-MS/MS测定每周1次的抗糖尿病药物DPP-4抑制剂；大鼠灌胃给药2 h后，测定血浆和脑组织中奥马瑞格列汀和曲瑞格列汀的浓度。用脑/血浆浓度比推算透过血脑屏障的渗透力。结果表明，只有奥马利普汀由于其低分子量和亲脂性而穿过血脑屏障，表明其作为抗帕金森病药物被重新定位。血脑屏障交叉的结果将会引起对帕金森氏症感兴趣的研究人员的兴趣。以十二烷基硫酸钠为表面活性剂，制备了一种新型鼻腔制剂，用于增溶具有促透和抗菌作用的亲脂性奥马利汀。鼻腔给药显示，与口服组相比，脑/血浆比增加了3.3倍，同时脑内胰高血糖素样肽-1浓度与对照组相比增加了2.6倍。
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work. LC-MS/MS determination of once-weekly anti-diabetic DPP-4 inhibitors; omarigliptin & trelagliptin in plasma and brain tissue was employed after 2 h of oral administration to rats. The brain/plasma concentration ratio was used to deduce the penetration power through the BBB. Results showed that only omarigliptin crossed the BBB due to its low molecular weight & lipophilic properties suggesting its repositioning as antiparkinsonian agent. The results of BBB crossing will be of interest for researchers interested in Parkinson’s disease. A novel intranasal formulation was developed using sodium lauryl sulphate surfactant to solubilize the lipophilic omarigliptin with penetration enhancing & antimicrobial properties. Intranasal administration showed enhanced brain/plasma ratio by 3.3 folds compared to the oral group accompanied with 2.6 folds increase in brain glucagon-like peptide-1 concentration compared to the control group.
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DOI：
10.3390/ph6101304
发表时间：
2013-10-11
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Corbett A;Williams G;Ballard C
通讯作者：
Ballard C
影响因子：
4.7
作者：
Abdelsalam, Rania M.;Safar, Marwa M.
通讯作者：
Safar, Marwa M.
影响因子：
5.8
作者：
Badawi, Ghada A.;Abd El Fattah, Mai A.;El Sayed, Moushira I.
通讯作者：
El Sayed, Moushira I.
影响因子：
11.5
作者：
Burness, Celeste B.
通讯作者：
Burness, Celeste B.
影响因子：
3.3
作者：
Breen, Kieran C.;Drutyte, Gerda
通讯作者：
Drutyte, Gerda