Venlafaxine hydrochloride is an orally active serotonin-norepinephrine reuptake inhibitor (SNRIs) with Ki values of 2480nM and 82nM for ligand binding to human NE and 5-HT transporters, respectively[1]. Venlafaxine hydrochloride has been used clinically as an antidepressant[2-3].
In vitro, treatment of BV-2 cells with Venlafaxine hydrochloride (0.01-1mM) for 24 hours showed mild survival impairment only at high non-physiological concentrations (1mM), with no cytotoxicity at other concentrations, and only slightly inhibited nitric oxide (NO) production in BV-2 cells stimulated by LPS (1μg/ml) [4]. Treatment of human colon cancer cells (HCT116 and SW480) with Venlafaxine hydrochloride (10μM) for 24-72 hours antagonized the effect of NE by inhibiting NET expression, thereby inhibiting the progression of colon cancer[5].
In vivo, Venlafaxine hydrochloride (1mg/100g; 2mg/ml; 28 days; i.p.) in a SD rat depression model increased the expression level of BDNF in the rat hippocampus by affecting the PI3k/PKB/eNOS pathway, repaired the damaged pyramidal cell layer of the hippocampus, and effectively improved the behavioral ability of depressed rats[6]. Venlafaxine hydrochloride (40-60mg/kg; 1-3h; i.p.) effectively relieved neuropathic pain induced by Oxaliplatin injection in mice by activating spinal cord α2-adrenergic receptors[7].
References:
[1]. Bymaster F P, Dreshfield-Ahmad L J, Threlkeld P G, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors[J]. Neuropsychopharmacology, 2001, 25(6): 871-880.
[2]. Schweizer E, Thielen R J, Frazer A. Venlafaxine: a novel antidepressant compound[J]. Expert opinion on investigational drugs, 1997, 6(1): 65-78.
[3]. Daiss J O, Burschka C, Mills J S, et al. Sila-venlafaxine, a sila-analogue of the serotonin/noradrenaline reuptake inhibitor venlafaxine: synthesis, crystal structure analysis, and pharmacological characterization[J]. Organometallics, 2006, 25(5): 1188-1198.
[4]. Dubovický M, Császár E, Melicherčíková K, et al. Modulation of microglial function by the antidepressant drug venlafaxine[J]. Interdisciplinary toxicology, 2014, 7(4): 201-207.
[5]. Zhang H, Han J, Zhang J, et al. Venlafaxine antagonizes the noradrenaline-promoted colon cancer progression by inhibiting the norepinephrine transporter[J]. Cell death discovery, 2023, 9(1): 152.
[6]. Huang X, Mao Y S, Li C, et al. Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain-derived neurotrophic factor in a rat depression model[J]. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 2014, 69(12): 909-916.
[7]. Li D, Lee J H, Choi C W, et al. The analgesic effect of venlafaxine and its mechanism on oxaliplatin-induced neuropathic pain in mice[J]. International Journal of Molecular Sciences, 2019, 20(7): 1652.
Venlafaxine hydrochloride是一种具有口服活性的5-羟色胺和去甲肾上腺素再摄取抑制剂 （SNRIs; Serotonin-norepinephrine reuptake inhibitors），对配体与人NE和5-HT转运蛋白结合的Ki值分别为2480nM和82nM[1]。Venlafaxine hydrochloride已作为临床抗抑郁药物进行使用[2-3]。
在体外，Venlafaxine hydrochloride（0.01-1mM）处理BV-2细胞24小时，仅在高非生理浓度（1mM）下观察到轻度存活损伤，其余浓度没有细胞毒性，且仅对LPS（1μg/ml）刺激BV-2细胞产生的一氧化氮（NO）产生轻微抑制作用[4]。Venlafaxine hydrochloride（10μM）处理人结肠癌细胞（HCT116和SW480）24-72小时，通过抑制NET表达拮抗NE的作用，抑制结肠癌的进展[5]。
在体内，Venlafaxine hydrochloride（1mg/100g; 2mg/ml; 28 days; i.p.）处理SD大鼠抑郁模型，通过影响PI3k/PKB/eNOS通路提高了大鼠海马中BDNF的表达水平，修复了受损的海马体锥体细胞层，有效改善了抑郁大鼠的行为能力[6]。Venlafaxine hydrochloride（40-60mg/kg; 1-3h; i.p.）通过激活脊髓α2-肾上腺素能受体有效缓解了小鼠因注射Oxaliplatin引起的神经性疼痛[7]。