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.