Urethane (Carbamic acid ethyl ester)

Urethane (Carbamic acid ethyl ester) is an organic compound with an ester structure, which can be used for the synthesis of polyurethane materials^[1], and has also been used as an anesthetic for intravenous injection^[2]. Urethane exerts its sedative, analgesic, and general anesthetic effects by inhibiting the transmission of nerve signals in the central nervous system, reducing the excitability of nerve cells^[3]. However, Urethane has potential carcinogenicity, and long-term exposure or excessive intake can increase the risk of tumor occurrence in organs such as the liver and kidneys, and may also have adverse effects on the reproductive system^[4].

In vitro, Urethane (10mM) perfused rat visual cortical neurons for 10min–2h, followed by depolarizing current stimulation for 1s, significantly inhibited action potential discharge and decreased membrane resistance^[5]. Urethane (0.4%) treated normal mouse somatic cells (including fibroblasts and epithelial cells) and tumor cells (C57 sarcoma and adenocarcinoma 63 malignant cells) for 2 to 4 days, significantly inhibited the growth and mitosis of normal cells, reducing the mitosis rate by about 50%. However, Urethane significantly promoted the growth and mitosis of tumor cells, increasing the mitosis rate by 2 to 4 times^[6].

In vivo, Urethane (1.25–1.5g/kg) was administered intraperitoneally to anesthetize 3–4-month-old Sprague-Dawley rats, significantly inducing glutamate overflow in different brain regions^[7]. Urethane (1g/kg) was administered intraperitoneally to FVB, BALB/c, and C57B6 mice, with susceptible strains (FVB, BALB/c) showing early NF-κB activation and lung inflammation, while the resistant strain (C57B6) failed to activate NF-κB or induce lung inflammation^[8].

References:
[1] Szelest-Lewandowska A, Masiulanis B, Szymonowicz M, et al. Modified polycarbonate urethane: synthesis, properties and biological investigation in vitro. J Biomed Mater Res A. 2007 Aug;82(2):509-20.
[2] Carter DA, Dyer RG. Inhibition by pentobarbitone and urethane of the in vitro response of the adenohypophysis to luteinising hormone-releasing hormone in male rats. Br J Pharmacol. 1979 Oct;67(2):277-81.
[3] Mondino A, González J, Li D, et al. Urethane anaesthesia exhibits neurophysiological correlates of unconsciousness and is distinct from sleep. Eur J Neurosci. 2024 Feb;59(4):483-501.
[4] Sotomayor RE, Collins TF. Mutagenicity, metabolism, and DNA interactions of urethane. Toxicol Ind Health. 1990 Jan;6(1):71-108.
[5] Sceniak MP, Maciver MB. Cellular actions of urethane on rat visual cortical neurons in vitro. J Neurophysiol. 2006 Jun;95(6):3865-74.
[6] LASNITZKI I. Some effects of urethane on the growth and mitosis of normal and malignant cells in vitro. Br J Cancer. 1949 Dec;3(4):501-9.
[7] Beitchman JA, Krishna G, Bromberg CE, et al. Effects of isoflurane and urethane anesthetics on glutamate neurotransmission in rat brain using in vivo amperometry. BMC Neurosci. 2023 Oct 10;24(1):52.
[8] Stathopoulos GT, Sherrill TP, Cheng DS, et al. Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18514-9.

Urethane (Carbamic acid ethyl ester)是一种具有酯类结构的有机化合物，可用于合成聚氨酯类材料^[1]，也曾作为通过静脉注射使用的麻醉剂^[2]。Urethane通过抑制中枢神经系统的神经信号传递，降低神经细胞兴奋性，从而发挥镇静、镇痛及全身麻醉效果^[3]。但是Urethane具有潜在致癌性，长期接触或过量摄入会增加肝脏、肾脏等器官的肿瘤发生风险，且可能对生殖系统产生不良影响^[4]。

在体外，Urethane（10mM）灌流大鼠视觉皮层神经元10min–2h，随后以去极化电流刺激1s，Urethane显著抑制动作电位放电，同时降低膜电阻^[5]。Urethane（0.4%）处理小鼠正常体细胞（包括成纤维细胞和上皮细胞）和肿瘤细胞（C57肉瘤和腺癌63恶性细胞）2至4天，对正常细胞的生长和有丝分裂有显著抑制作用，有丝分裂率降低约50%，但对肿瘤细胞的生长和有丝分裂有显著促进作用，有丝分裂率增加2至4倍^[6]。

在体内，Urethane（1.25–1.5g/kg）腹腔注射用于麻醉3–4月龄Sprague-Dawley大鼠，Urethane显著诱导了不同脑区的谷氨酸外溢^[7]。Urethane（1g/kg）腹腔注射处理FVB、BALB/c和C57B6小鼠，易感品系（FVB、BALB/c）表现出早期NF-κB激活和肺部炎症，而耐受品系（C57B6）未激活NF-κB或诱导肺部炎症^[8]。