RHC 80267 is a potent and selective diacylglycerol lipase (DAGL) inhibitor. RHC 80267 can also inhibit cholinesterase activity (IC₅₀= 4µM), suppress cyclooxygenase (COX) activity, and inhibit phosphatidylcholine hydrolysis[1-2]. RHC 80267 functions by inhibiting diacylglycerol lipase, and RHC 80267 can be used in research related to the nervous system, cardiovascular system, and metabolic diseases[3-4].
In vitro, RHC 80267 (100µM) was used to pretreat rat cortical astrocytes for 2-6 hours, followed by culture under combined glucose-oxygen deprivation conditions. RHC 80267 significantly inhibited ischemia-induced arachidonic acid metabolite release but exacerbated cellular damage[5]. RHC 80267 (10–100µM) was used to treat GH3 pituitary cells for 1-4 hours. RHC 80267 inhibited prolactin secretion from the cells and blocked potassium-stimulated calcium influx[6].
In vivo, in a mouse model of temporal lobe epilepsy induced by pilocarpine, RHC 80267 (1.3µmol/animal; for 7 consecutive days) was administered via intracerebroventricular injection. RHC 80267 significantly reduced the incidence and duration of spontaneous recurrent seizures during the chronic phase, improved anxiety- and depression-like behaviors, enhanced spatial learning and memory capacity, and inhibited neuronal loss in the hippocampal CA1 region[7].
References:
[1] Chuang M, Severson DL. Inhibition of diacylglycerol metabolism in isolated cardiac myocytes by U-57 908 (RHC 80267), a diacylglycerol lipase inhibitor. J Mol Cell Cardiol. 1990 Sep;22(9):1009-16.
[2] Sutherland CA, Amin D. Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267. J Biol Chem. 1982 Dec 10;257(23):14006-10.
[3] Ghisdal P, Vandenberg G, Hamaide MC, et al. The diacylglycerol lipase inhibitor RHC-80267 potentiates the relaxation to acetylcholine in rat mesenteric artery by anti-cholinesterase action. Eur J Pharmacol. 2005 Jul 4;517(1-2):97-102.
[4] Oglesby TD, Gorman RR. The inhibition of arachidonic acid metabolism in human platelets by RHC 80267, a diacylglycerol lipase inhibitor. Biochim Biophys Acta. 1984 Apr 18;793(2):269-77.
[5] Haun SE, Trapp VL, Clotz MA, et al. Nordihydroguaiaretic acid and RHC 80267 potentiate astroglial injury during combined glucose-oxygen deprivation. Mol Chem Neuropathol. 1995 May;25(1):35-49.
[6] Camoratto AM, Grandison L. Effects of RHC 80267, a diglyceride lipase inhibitor, on prolactin secretion and calcium uptake in GH3 pituitary cells. Life Sci. 1987 Jan 19;40(3):275-81.
[7] Ma L, Wang L, Yang F, et al. Disease-modifying effects of RHC80267 and JZL184 in a pilocarpine mouse model of temporal lobe epilepsy. CNS Neurosci Ther. 2014 Oct;20(10):905-15.
RHC 80267是一种有效的、选择性二酰基甘油脂酶（DAGL）抑制剂，RHC 80267还能够抑制胆碱酯酶活性（IC₅₀=4μM），可抑制环氧化酶（COX）活性和磷脂酰胆碱的水解[1-2]。RHC 80267通过抑制二酰基甘油脂酶发挥作用，RHC 80267可用于神经系统、心血管系统以及代谢疾病的相关研究[3-4]。
在体外，RHC 80267（100μM）预处理大鼠皮质星形胶质细胞2-6小时，随后在葡萄糖-氧气联合剥夺条件下培养，RHC 80267显著抑制缺血诱导的花生四烯酸代谢物释放，加剧细胞损伤[5]。RHC 80267（10–100μM）处理GH3垂体细胞1-4小时，RHC 80267可抑制细胞的泌乳素分泌，阻断钾离子刺激的钙内流[6]。
在体内，在中，RHC 80267（1.3μmol/只；持续7天）侧脑室注射处理Pilocarpine诱导颞叶癫痫模型小鼠，RHC 80267显著降低慢性期自发性复发癫痫的发生率及发作持续时间，并改善焦虑抑郁样行为、空间学习记忆能力，同时抑制海马CA1区神经元丢失[7]。