Metoclopramide is a potent 5-HT3 and dopamine D2 receptor antagonist with IC50 values of 308nM and 483nM, respectively[1]. Metoclopramide can be used in the study of nausea and vomiting, gastroesophageal reflux and gastroparesis[2]. Metoclopramide has the effect of stimulating serotonin receptors[3].
In vitro, Metoclopramide (0-10μM) treated mouse skin fibroblasts (L929 cells) for 6h effectively inhibited the potent apoptotic activity of paraoxon and malathion[4]. Metoclopramide (1μM) treated leukemia cell line (K562 cells) blocked CD93 signaling and reduced leukemia stem cell (LSC) function[5].
In vivo, Metoclopramide (10mg/kg) was injected subcutaneously to treat experimental abdominal sepsis in rats and had no adverse effects on the healing of intestinal anastomosis. The hydroxyproline level of the anastomosis was significantly reduced on the third day after surgery[6]. Metoclopramide (6.7mg/kg) was administered subcutaneously to unmated female Swiss ZH-1 mice for 50 days and significantly increased the number and volume of pituitary lactotrophs at all stages of the estrous cycle[7].
References:
[1] Hirokawa Y, Harada H, Yoshikawa T, et al. Synthesis and structure–activity relationships of 4-amino-5-chloro-N-(1, 4-dialkylhexahydro-1, 4-diazepin-6-yl)-2-methoxybenzamide derivatives, novel and potent serotonin 5-HT3 and dopamine D2 receptors dual antagonist[J]. Chemical and pharmaceutical bulletin, 2002, 50(7): 941-959.
[2] Lee A, Kuo B. Metoclopramide in the treatment of diabetic gastroparesis[J]. Expert review of endocrinology & metabolism, 2010, 5(5): 653-662.
[3] Guillemot J, Compagnon P, Cartier D, et al. Metoclopramide stimulates catecholamine-and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors[J]. Endocrine-Related Cancer, 2009, 16(1): 281.
[4] Jaber B M, Petroianu G A, Rizvi S A, et al. Protective effect of metoclopramide against organophosphate‐induced apoptosis in the murine skin fibroblast L929[J]. Journal of Applied Toxicology, 2018, 38(3): 329-340.
[5] Riether C, Radpour R, Kallen N M, et al. Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells[J]. Cell reports, 2021, 34(4).
[6] e Silva S M, Carneiro F P, Ferreira V M M, et al. Effects of metoclopramide on healing of colonic anastomoses in a rat model of abdominal sepsis[J]. Journal of Investigative Surgery, 2013, 26(5): 235-241.
[7] Gomes R C T, Verna C, Simoes R S, et al. Effects of metoclopramide on the mouse anterior pituitary during the estrous cycle[J]. Clinics, 2011, 66: 1101-1104.
Metoclopramide（胃复安）是一种有效的5-HT3和多巴胺D2受体拮抗剂，IC50 值分别为308nM和483nM[1]。Metoclopramide可用于恶心呕吐、胃食管反流和胃轻瘫的研究[2]。Metoclopramide具有激动血清素受体的作用[3]。
在体外，Metoclopramide（0-10μM）处理小鼠皮肤成纤维细胞（L929细胞）6h，有效抑制了对氧磷和马拉硫磷的强效凋亡活性[4]。Metoclopramide（1μM）处理白血病细胞系（K562细胞），阻断了CD93信号传导，降低了白血病干细胞（LSC）功能[5]。
在体内，Metoclopramide（10mg/kg）通过皮下注射治疗实验性腹部脓毒症大鼠，对肠吻合口的愈合没有有害影响，术后第三天吻合口羟脯氨酸水平明显降低[6]。Metoclopramide（6.7mg/kg）通过皮下注射处理未交配的Swiss ZH-1品系雌性小鼠50天，在发情周期的所有阶段显著增加垂体催乳细胞的数量和体积[7]。