Mecamylamine hydrochloride is a non-selective, non-competitive nicotinic acetylcholine receptor (nAChR) antagonist that can block various nAChR subtypes, such as α3β4, α4β2, and α3β2 receptors, with IC50 values of 640nM, 2.5µM, and 3.6µM respectively[1]. Mecamylamine hydrochloride can inhibit acetylcholine in autonomic ganglia, thereby reducing blood pressure[2], and also has antidepressant functions[3]. Mecamylamine hydrochloride can also improve symptoms of diabetes[4].
In vitro, pre-treatment of SH-SY5Y neuroblastoma cells with Mecamylamine hydrochloride (10µM) for 1h, followed by stimulation with Nicotine (100µM) for 48h, significantly inhibited nicotine-induced cell proliferation and blocked the increase in BDNF secretion and TrkB receptor surface density induced by Nicotine[5]. Pre-treatment of GLC-8 small cell lung cancer cells with Mecamylamine hydrochloride (1µM) for 10min, followed by stimulation with Nicotine (100nM) for 5min, completely blocked the increase in nicotine-induced extracellular signal-regulated kinase (MAP kinase) activity[6].
In vivo, Mecamylamine hydrochloride (50mg/kg/day) was continuously administered via subcutaneously implanted osmotic pumps and used to treat mouse models of choroidal neovascularization for 2 weeks. Mecamylamine hydrochloride significantly inhibited Matrigel-induced and ocular endothelial cell tube formation in mice[7]. Pre-treatment of diabetic C57BL/6 mice with Mecamylamine hydrochloride (2mg/kg) via intraperitoneal injection for 3 weeks restored the mice's sensitivity to glucose and effectively reduced their hyperglycemia[8].
References:
[1] Kumar P, Scholze P, Fronius M, et al. Nicotine stimulates ion transport via metabotropic β4 subunit containing nicotinic ACh receptors. Br J Pharmacol. 2020 Dec;177(24):5595-5608.
[2] Shytle RD, Penny E, Silver AA, et al. Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens. 2002 Jul;16(7):453-7.
[3] Lippiello PM, Beaver JS, Gatto GJ, et al. TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity. CNS Neurosci Ther. 2008 Winter;14(4):266-77.
[4] Campochiaro PA, Shah SM, Hafiz G, et al. Topical mecamylamine for diabetic macular edema. Am J Ophthalmol. 2010 May;149(5):839-51.e1.
[5] Serres F, Carney SL. Nicotine regulates SH-SY5Y neuroblastoma cell proliferation through the release of brain-derived neurotrophic factor. Brain Res. 2006 Jul 26;1101(1):36-42.
[6] Cattaneo MG, D'atri F, Vicentini LM. Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells. Biochem J. 1997 Dec 1;328 ( Pt 2)(Pt 2):499-503.
[7] Kiuchi K, Matsuoka M, Wu JC, et al. Mecamylamine suppresses Basal and nicotine-stimulated choroidal neovascularization. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1705-11.
[8] Fernández-Cabezudo MJ, George JA, Bashir G, et al. Involvement of Acetylcholine Receptors in Cholinergic Pathway-Mediated Protection Against Autoimmune Diabetes. Front Immunol. 2019 May 15;10:1038.
Mecamylamine hydrochloride是一种非选择性、非竞争性的烟碱型乙酰胆碱受体（nAChR）拮抗剂，能够阻断多种不同的nAChR亚型，如α3β4、α4β2、α3β2，其IC50值分别为640nM、2.5µM、3.6µM[1]。Mecamylamine hydrochloride可以抑制自主神经节中的乙酰胆碱，从而降低血压[2]，以及发挥抗抑郁的功能[3]。Mecamylamine hydrochloride还可改善糖尿病的症状[4]。
在体外，Mecamylamine hydrochloride（10μM）预处理SH-SY5Y神经母细胞瘤细胞1h，随后以尼古丁（100μM）刺激48 h，Mecamylamine hydrochloride显著抑制尼古丁诱导的细胞增殖，同时阻断尼古丁对BDNF分泌和TrkB受体细胞表面密度的增加[5]。Mecamylamine hydrochloride（1μM）预处理GLC-8小细胞肺癌细胞10min，随后以尼古丁（100nM）刺激5min，Mecamylamine hydrochloride完全阻断尼古丁诱导的细胞外信号调节激酶（MAP激酶）活性的增加[6]。
在体内，Mecamylamine hydrochloride（50mg/kg/天）通过皮下植入的渗透泵持续给药，用于处理脉络膜新生血管形成的小鼠模型2周。Mecamylamine hydrochloride显著抑制了小鼠的基质胶和眼内皮细胞管形成[7]。Mecamylamine hydrochloride（2mg/kg）通过腹腔注射预处理糖尿病C57BL/6小鼠3周后，Mecamylamine hydrochloride恢复了小鼠对于葡萄糖的敏感性，并且可有效降低小鼠的高血糖[8]。