Agomelatine is a melatonin (MT) receptor agonist with Ki values of 0.1 nM and 0.12 nM for MT1 and MT2, respectively[1]. Agomelatine is also a 5-hydroxytryptamine (5-HT) receptor antagonist with Ki values of 631 nM and 660 nM for 5-HT2C and 5-HT2B respectively[2]. Agomelatine can regulate circadian rhythm and enhance mood, and is used in research on major depressive disorder (MDD) [3].
In vitro, Agomelatine (10, 20 μM) treated endothelial cells and monocytes for 24 h, dose-dependently inhibited the angiotensin II-induced increase in the expression of AT1R, VCAM-1 and ICAM-1 and reduced cell adhesion [4]. Agomelatine (8, 16 μM) treated hippocampal neuron HT22 cells for 24 hours, inhibited the neurotoxicity caused by cisplatin injury, and attenuated oxidative stress and inflammatory response [5].
In vivo, Agomelatine (40mg/kg) was treated by intraperitoneal injection in rats with LPS-induced depression and significantly improved the rats' anxiety and depression-like behaviors, reducing neuroinflammation and neuronal damage[6]. Agomelatine (25, 50 or 75 mg/kg; ip) has antioxidant activity in a mouse seizure model [7].
References:
[1] Dridi D, Zouiten A, Mansour H B. Depression: chronophysiology and chronotherapy[J]. Biological rhythm research, 2014, 45(1): 77-91.
[2] Millan M J, Gobert A, Lejeune F, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways[J]. Journal of Pharmacology and Experimental Therapeutics, 2003, 306(3): 954-964.
[3] Smeraldi E, Delmonte D. Agomelatine in depression[J]. Expert opinion on drug safety, 2013, 12(6): 873-880.
[4] Hong N, Ye Z, Lin Y, et al. Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion[J]. Aging (albany NY), 2021, 13(14): 18515.
[5] Cankara F N, Günaydın C, Çelik Z B, et al. Agomelatine confers neuroprotection against cisplatin-induced hippocampal neurotoxicity[J]. Metabolic brain disease, 2021, 36(2): 339-349.
[6] Lan T, Wu Y, Zhang Y, et al. Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway[J]. Journal of neuroinflammation, 2022, 19(1): 117.
[7] Aguiar C C T, Almeida A B, Araújo P V P, et al. Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures[J]. Cellular and molecular neurobiology, 2013, 33: 825-835.
Agomelatine是一种褪黑素（MT）受体激动剂，对MT1和MT2的Ki值分别为0.1 nM和0.12 nM[1]。Agomelatine也是一种5-羟色胺（5-HT）受体拮抗剂，对5-HT2C 和5-HT2B 的Ki值分别为631 nM和660 nM[2]。Agomelatine可以调节昼夜节律和提升情绪，应用于重度抑郁症（MDD）研究[3]。
在体外，Agomelatine（10、20μM）处理内皮细胞和单核细胞24h，剂量依赖性地抑制了血管紧张素II诱导的AT1R、VCAM-1和ICAM-1的表达增加，减少了细胞粘附[4]。Agomelatine（8、16μM）处理海马神经元HT22细胞24h，抑制了顺铂损伤引起的神经毒性，减弱了氧化应激和炎症反应[5]。
在体内，Agomelatine（40mg/kg）通过腹膜注射治疗LPS诱导的抑郁症大鼠，显著改善了大鼠的焦虑和抑郁样行为，减轻了神经炎症和神经元损伤[6]。Agomelatine (25、50或75 mg/kg；ip) 在小鼠癫痫发作模型中具有抗氧化活性[7]。