Escitalopram

Escitalopram is a highly selective serotonin reuptake inhibitor (K_i=0.89nM). Escitalopram increases serotonin concentration in the central nervous system by highly selectively inhibiting the serotonin transporter, while exhibiting weak effects on norepinephrine and dopamine reuptake. Escitalopram can be used in research related to depression, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder^[1-4].

In vitro, HEK293/tau441 cells pre-incubated with Forskolin (4μM) for 2 hours were treated with Escitalopram (20–80μM) for 22 hours. Escitalopram significantly alleviated tau hyperphosphorylation at Ser214 and Ser198/199/202 sites, while increasing the levels of serine-9-phosphorylated GSK-3β and Ser473-phosphorylated Akt^[5]. Rat B104, human SH-SY5Y, IMR32, and Kelly neuroblastoma cell lines were treated with Escitalopram (25–175μM). Escitalopram significantly reduced cell viability and down-regulated the expression of poor prognosis factors for neuroblastoma, including MYBL2, BIRC5, and BARD1^[6].

In vivo, SCID mice bearing Huh-7 cell xenograft tumors were orally administered Escitalopram (12.5mg/kg) once daily for 4 weeks. Escitalopram significantly reduced tumor volume^[7]. Obsessive-compulsive disorder model Wistar rats were intraperitoneally injected with Escitalopram (10mg/kg/day) once daily for 7 days. Escitalopram significantly increased GDNF and BDNF levels in serum and brain tissues, as well as brain 5-HT content^[8].

References:
[1] Zhang P, Cyriac G, Kopajtic T, et al. Structure-activity relationships for a novel series of citalopram (1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile) analogues at monoamine transporters. J Med Chem. 2010 Aug 26;53(16):6112-21.
[2] Pastoor D, Gobburu J. Clinical pharmacology review of escitalopram for the treatment of depression. Expert Opin Drug Metab Toxicol. 2014 Jan;10(1):121-8.
[3] Wu C, Gong WG, Wang YJ, et al. Escitalopram alleviates stress-induced Alzheimer's disease-like tau pathologies and cognitive deficits by reducing hypothalamic-pituitary-adrenal axis reactivity and insulin/GSK-3β signal pathway activity. Neurobiol Aging. 2018 Jul;67:137-147.
[4] Cirrito JR, Wallace CE, Yan P, et al. Effect of escitalopram on Aβ levels and plaque load in an Alzheimer mouse model. Neurology. 2020 Nov 10;95(19):e2666-e2674.
[5] Ren QG, Wang YJ, Gong WG, et al. Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells. J Mol Neurosci. 2015 Jun;56(2):500-8.
[6] Sakka L, Delétage N, Chalus M, et al. Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation. Oncotarget. 2017 Jun 27;8(26):42789-42807.
[7] Chen LJ, Hsu TC, Chan HL, et al. Protective Effect of Escitalopram on Hepatocellular Carcinoma by Inducing Autophagy. Int J Mol Sci. 2022 Aug 17;23(16):9247.
[8] Guo HR, Huang BL, Wang YL, et al. Effect of Escitalopram on Serum GDNF and BDNF Levels and 5-HT Level of Brain Tissue of Obsessive-Compulsive Disorder Rats. Cell Mol Neurobiol. 2020 Aug;40(6):991-997.

Escitalopram是一种高选择性的5-羟色胺再摄取抑制剂（K_i=0.89nM）。Escitalopram通过高度选择性抑制5-HT转运体来增加中枢神经系统5-羟色胺浓度，同时对去甲肾上腺素和多巴胺再摄取作用微弱。Escitalopram可用于抑郁症、惊恐障碍、广泛性焦虑症和强迫症的相关研究^[1-4]。

在体外，Escitalopram（20–80μM）处理经Forskolin（4μM）预孵育2小时的HEK293/tau441细胞22小时。Escitalopram显著减轻tau在Ser214和Ser198/199/202位点的过度磷酸化，同时增加serine-9-phosphorylated GSK-3β和Ser473磷酸化Akt的水平^[5]。Escitalopram（25–175μM）处理大鼠B104、人SH-SY5Y、IMR32和Kelly神经母细胞瘤细胞系。Escitalopram显著降低细胞活力，下调MYBL2、BIRC5、BARD1等神经母细胞瘤不良预后因子的表达^[6]。

在体内，Escitalopram（12.5mg/kg）每天一次口服灌胃于携带Huh-7细胞异种移植肿瘤的SCID小鼠，连续4周。Escitalopram显著减小了肿瘤体积^[7]。Escitalopram（10mg/kg/day）每天一次腹腔注射于强迫症模型Wistar大鼠，持续7天。Escitalopram显著增加了小鼠血清和脑组织中的GDNF和BDNF水平以及脑组织5-HT含量^[8]。