Dextromethorphan (hydrobromide hydrate) is a D-isomer of levorphanol, similar to codeine. Unlike several other morphine derivatives, Dextromethorphan does not cause opioid activity [1]. Dextromethorphan is a conformational antagonist and voltage-dependent antagonist of N-methyl D-aspartate (NMDA) control ion channels [2]. Due to its strong antitussive effect, Dextromethorphan is widely used as a cough suppressant. Dextromethorphan has been used in multimodal analgesic treatment for acute and neuropathic pain [3-4].
In vitro, Dextromethorphan (12.5, 25, 50 and 100μM; 18h) dose-dependently inhibited the expression of co-stimulatory molecules (CD80, CD86 and CD40) in LPS-induced mouse bone marrow-derived dendritic cells (BMDCs), and reduced the production of reactive oxygen species, pro-inflammatory cytokines and chemokines in the cells [5]. Under an intracellular/extracellular pH gradient of 5.5/7.3, Dextromethorphan (0-100μM; 10min) reversibly inhibited the voltage-gated proton current in BV2 microglial cells, with an IC50 of 51.7μM [6].
In vivo, Dextromethorphan (1 and 3mg/ml; 8 weeks; orally in drinking water) long-term treatment significantly improved the plasma insulin concentration, glucose tolerance and islet cell quality of 2-type diabetic (T2DM) mice [7]. Dextromethorphan (32mg/kg/day; single-dose; i.p.) pretreatment for 30min produced a similar antidepressant effect in C57BL/6 mice in the tail suspension test (TST), but failed to produce a similar antidepressant effect 24 hours after administration [8].
References:
[1] Mayet S. Atypical opioids[J]. Southern African Journal of Anaesthesia and Analgesia, 2023: 147-152.
[2] Werling L L, Lauterbach E C, Calef U. Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action[J]. The neurologist, 2007, 13(5): 272-293.
[3] Bolser, D.C., Aziz, S.M., DeGennaro, F.C., et al. Antitussive effects of GABAB agonists in the cat and guinea-pig. Br. J. Pharmacol. 110(1), 491-495 (1993).
[4] Chen, Y.W., Chu, K.S., Lin, C.N., et al. Dextromethorphan or dextrorphan have a local anesthetic effect on infiltrative cutaneous analgesia in rats. Anesth. Analg. 104(5), 1251-1255 (2007).
[5] Chen D Y, Song P S, Hong J S, et al. Dextromethorphan inhibits activations and functions in dendritic cells[J]. Journal of Immunology Research, 2013, 2013(1): 125643.
[6] Song JH, Yeh JZ. Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells. Neurosci Lett. 2012;516(1):94-98.
[7] Marquard J, Otter S, Welters A, et al. Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment[J]. Nature medicine, 2015, 21(4): 363-372.
[8] Saavedra JS, Garrett PI, Honeycutt SC, Peterson AM, White JW, Hillhouse TM. Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice. Pharmacol Biochem Behav. 2020;197:173003.
Dextromethorphan (hydrobromide hydrate)是一种与可待因类似的levorphanol的D型异构体。Dextromethorphan不像其他几种吗啡衍生物那样引起阿片类活性 [1]。Dextromethorphan是N-甲基 D-天冬氨酸（NMDA）控制离子通道的变构拮抗剂和电压依赖性通道的拮抗剂 [2]。由于其强烈的止咳作用，Dextromethorphan被广泛用作咳嗽抑制剂。Dextromethorphan已用于急性和神经性疼痛的多模态镇痛治疗[3-4]。
在体外，Dextromethorphan（12.5, 25, 50和100μM; 18h）处理剂量依赖性地抑制了LPS诱导的小鼠骨髓源性树突状细胞（BMDCs）中共刺激分子（CD80、CD86和CD40）的表达，减少了细胞中活性氧、促炎细胞因子和趋化因子的产生 [5]。在细胞内/细胞外pH梯度为5.5/7.3的情况下，Dextromethorphan(0-100μM; 10min)可逆地抑制小胶质细胞BV2细胞中电压门控质子电流，IC50为51.7μM [6]。
在体内，Dextromethorphan（1和3mg/ml; 8 weeks; drinking water orally）长期治疗显著改善了2型糖尿病（T2DM）小鼠的血浆胰岛素浓度和葡萄糖耐量和胰岛细胞质量 [7]。Dextromethorphan（32mg/kg/day; single-dose; i.p.）预处理30min对尾部悬浮试验（TST）中的C57BL/6小鼠产生类似抗抑郁作用，但在给药24小时后未能产生类似抗抑郁作用 [8]。