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Papers of the Week


Papers: 31 Aug 2024 - 6 Sep 2024


2024 Aug 14


Int J Mol Sci


39201526


25


16

Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain.

Authors

Babkov D, Eliseeva N, Adzhienko K, Bagmetova V, Danilov D, McReynolds CB, Morisseau C, Hammock BD, Burmistrov V

Abstract

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund’s adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound (1,1′-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose ( < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes a promising candidate for further structure optimization and preclinical evaluation.