更新于：2024-12-21
Doxepin hydrochloride
盐酸多塞平
更新于：2024-12-21
概要
基本信息
简介多塞平是一种小分子药物，作为一种有效的治疗剂，靶向去甲肾上腺素转运蛋白 (NET) 和血清素转运蛋白亚型 5 (SERT-5)。通过抑制大脑中去甲肾上腺素和 5-羟色胺再摄取的双重作用，多塞平起到了出色的抗抑郁药的作用，导致突触间隙内这些神经递质的水平升高。这种神经化学改变有助于稳定情绪、减轻焦虑和提高睡眠质量，从而产生许多好处。自 1969 年 9 月问世以来，多塞平一直是那些与抑郁症、焦虑症和失眠症作斗争的人们的希望灯塔。尽管如此，必须认识到多塞平会引起一些不良反应，包括但不限于嗜睡、口干、便秘和体重增加，甚至可能与其他药物相互作用。因此，明智的做法是在医疗保健专家的指导下谨慎使用多塞平。 |
药物类型 小分子化药 |
别名 Doxepin、Doxepin hydrochloride (USP)、Doxepin Hydrochloride Cream + [16] |
作用机制 NET抑制剂(去甲肾上腺素转运蛋白抑制剂)、5-羟色胺重摄取抑制剂 |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评- |
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结构
分子式C19H22ClNO |
InChIKeyMHNSPTUQQIYJOT-UHFFFAOYSA-N |
CAS号1229-29-4 |
关联
33
项与 盐酸多塞平 相关的临床试验评价盐酸多塞平口颊膜治疗失眠障碍患者疗效和安全性的多中心Ⅲ期临床研究
- P23-01
A Triple-Blinded, Randomized, Placebo-Controlled Trial to Examine the Safety and Efficacy of Doxepin Rinse in Managing Oral Mucositis in Children Older than 7 Years of Age Receiving Chemotherapy
100 项与 盐酸多塞平 相关的临床结果
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100 项与 盐酸多塞平 相关的转化医学
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100 项与 盐酸多塞平 相关的专利（医药）
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1,365
项与 盐酸多塞平 相关的文献（医药）2024-11-19ACS Omega
Ni(0)-Catalyzed Efficient, Regioselective Synthesis of Dibenzo[b,e]oxepines and Dibenzo[c,f][1,2]oxathiepine 6,6-Dioxides: Mechanistic Study by DFT Calculation and Docking Interactions
Article
作者: Ghosh, Tapas ; Ahamed, Sk Shamim ; Mandal, Uma Sankar ; Manna, Debashree ; Lo, Rabindranath
Herein, a nickel-catalyzed divergent reductive-Heck reaction of 1-bromo-2-((2-(aryl/alkyl ethynyl)phenoxy)methyl)benzene and 2-(aryl/alkyl ethynyl)phenyl 2-bromobenzenesulfonate derivatives has been demonstrated through the regulation of reducing agents and solvent systems. This scalable protocol offers regio- and stereoselective access to functionalized dibenzo[b,e]oxepine and dibenzo[c,f][1,2]oxathiepine 6,6-dioxide scaffolds in high to excellent yields under a mild set of reaction conditions. This methodology offers a predictable route for the synthesis of medium ring oxygen heterocycles and demonstrates wide substrate scope and outstanding tolerance to various functional groups like hydroxyl and, of course, practical instance via the synthesis of doxepin and nordoxepin molecules. We validate the experimentally proposed reaction mechanism using the density functional theory method. Further, molecular docking interactions were investigated accommodating some of our synthesized molecules.
2024-09-01CLINICAL TOXICOLOGY
Evolving trends of pharmaceutical poisonings associated with QRS complex prolongation
Article
作者: Burns, Michele M. ; Simpson, Michael D. ; Tang, Katherine B.
INTRODUCTION:
Tricyclic antidepressants often cause drug-induced QRS complex prolongation in overdose but are now less commonly prescribed. We sought to determine, among a contemporary cohort of patients, the pharmaceuticals independently associated with QRS complex prolongation in acute overdose.
METHODS:
We performed secondary analysis of data from the Toxicology Investigators Consortium (ToxIC) Core Registry. We included adult patients presenting from January 2016 through March 2023 with acute or acute-on-chronic pharmaceutical exposures. The primary outcome was QRS complex prolongation >0.12 s. Secondary outcomes included cardiac arrest, death, ventricular dysrhythmia, intensive care unit admission, initiation of vasopressors, and treatment with sodium bicarbonate. We used a multivariable logistic regression model with QRS complex prolongation as the outcome and individual pharmaceuticals of interest as independent variables. We assessed yearly trends of the contribution of relevant pharmaceuticals to QRS complex prolongation since 2016.
RESULTS:
Of 11,945 patients in the total cohort (median age 37 years, 6,652 [55.7%] female), 366 (3.1%) developed QRS complex prolongation. Of 9,417 patients included in the model, 290 (3.1%) developed QRS complex prolongation. Amitriptyline, nortriptyline, doxepin, imipramine, noxiptiline, bupropion, flecainide, carvedilol, propranolol, diphenhydramine, and lamotrigine poisonings were independent predictors of QRS complex prolongation. Flecainide poisoning conferred the greatest odds of QRS complex prolongation (OR 574.1; 95% CI: 88.3-12,747). The contribution of tricyclic antidepressants to QRS complex prolongation decreased from 38.8% to 17.6% of all patients with QRS complex prolongation from 2016 to 2022. In 2022, the proportion of QRS complex prolongation from diphenhydramine (20.6%) surpassed that of tricyclic antidepressants.
DISCUSSION:
This study provides insights into contemporary pharmaceutical poisoning associated with QRS complex prolongation. Tricyclic antidepressants remain clinically relevant exposures but are no longer the most common cause of drug-induced QRS complex prolongation.
CONCLUSIONS:
Bupropion, diphenhydramine, and antidysrhythmics are increasingly common causes of QRS complex prolongation, each associated with numerous severe outcomes in poisoning. Greater safety measures to protect patients from cardiovascular toxicity from these pharmaceuticals are warranted.
2024-09-01JOURNAL OF MOLECULAR RECOGNITION
Binding characteristics of the doxepin E/Z‐isomers to the histamine H1 receptor revealed by receptor‐bound ligand analysis and molecular dynamics study
Article
作者: Kaneko, Hiroto ; Shiroishi, Mitsunori ; Nakamura, Ryota ; Kawai, Shinnosuke ; Korenaga, Ryunosuke ; Ando, Tadashi
Abstract:
Doxepin is an antihistamine and tricyclic antidepressant that binds to the histamine H1 receptor (H1R) with high affinity. Doxepin is an 85:15 mixture of the E‐ and Z‐isomers. The Z‐isomer is well known to be more effective than the E‐isomer, whereas based on the crystal structure of the H1R/doxepin complex, the hydroxyl group of Thr1123.37 is close enough to form a hydrogen bond with the oxygen atom of the E‐isomer. The detailed binding characteristics and reasons for the differences remain unclear. In this study, we analyzed doxepin isomers bound to the receptor following extraction from a purified H1R protein complexed with doxepin. The ratio of the E‐ and Z‐isomers bound to wild‐type (WT) H1R was 55:45, indicating that the Z‐isomer was bound to WT H1R with an approximately 5.2‐fold higher affinity than the E‐isomer. For the T1123.37V mutant, the E/Z ratio was 89:11, indicating that both isomers have similar affinities. Free energy calculations using molecular dynamics (MD) simulations also reproduced the experimental results of the relative binding free energy differences between the isomers for WT and T1123.37V. Furthermore, MD simulations revealed that the hydroxyl group of T1123.37 did not form hydrogen bonds with the E‐isomer, but with the adjacent residues in the binding pocket. Analysis of the receptor‐bound doxepin and MD simulations suggested that the hydroxyl group of T1123.37 contributes to the formation of a chemical environment in the binding pocket, which is slightly more favorable for the Z‐isomer without hydrogen bonding with doxepin.
100 项与 盐酸多塞平 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 入睡和睡眠障碍 | 美国 | 2010-03-17 | |
| 特应性皮炎 | 美国 | 1994-04-01 | |
| 神经性皮炎 | 美国 | 1994-04-01 | |
| 瘙痒 | 美国 | 1994-04-01 | |
| 焦虑症 | 美国 | 1969-09-23 | |
| 抑郁症 | 美国 | 1969-09-23 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 头颈部肿瘤 | 临床3期 | 美国 | 2010-12-01 | |
| 粘膜炎 | 临床3期 | 美国 | 2010-12-01 | |
| 疼痛 | 临床3期 | 美国 | 2010-12-01 | |
| 辐射损伤 | 临床3期 | 美国 | 2010-12-01 | |
| 口腔炎 | 临床3期 | 美国 | 2010-12-01 | |
| 食管癌 | 临床2期 | 美国 | 2014-04-14 | |
| 食管炎 | 临床2期 | 美国 | 2014-04-14 | |
| 下咽癌 | 临床2期 | 美国 | 2014-04-14 | |
| 喉肿瘤 | 临床2期 | 美国 | 2014-04-14 | |
| 淋巴瘤 | 临床2期 | 美国 | 2014-04-14 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 5 | placebo | 構蓋鑰醖鹹築鑰醖憲淵(衊襯鹽鏇顧簾憲觸遞簾) = 選壓鏇願積蓋餘願廠鬱 艱鑰顧夢艱齋範鏇網構 (醖窪範糧鹹餘網鹹窪窪, 醖廠範鏇醖鏇廠繭夢襯 ~ 窪獵醖淵淵鬱廠壓積築) 更多 | - | 2019-10-01 | ||
临床3期 | 155 | Placebo+Doxepin (Arm I (Doxepin-Placebo)) | 齋遞願壓夢範顧願醖鹽(構遞憲構餘淵糧觸壓製) = 夢網願願網蓋醖餘鏇鹹 鏇鏇襯製蓋醖遞繭鹽顧 (網築壓範艱獵蓋築遞衊, 蓋醖積襯鏇襯艱範糧鏇 ~ 鹹願鹽憲鹹範製構醖築) 更多 | - | 2017-05-08 | ||
Placebo+Doxepin (Arm II (Placebo-Doxepin)) | 齋遞願壓夢範顧願醖鹽(構遞憲構餘淵糧觸壓製) = 觸築構鹹鏇糧夢餘願範 鏇鏇襯製蓋醖遞繭鹽顧 (網築壓範艱獵蓋築遞衊, 構鑰顧顧衊顧築蓋遞淵 ~ 繭衊齋網願積鏇鹽衊築) 更多 | ||||||
N/A | - | 膚範艱蓋構鏇願鏇積顧(糧襯襯鑰壓齋選觸衊膚) = 窪積淵遞膚醖觸糧壓艱 積廠遞鏇選廠壓衊餘簾 (餘願憲鑰獵網窪艱艱鬱 ) | 积极 | 2016-10-01 | |||
膚範艱蓋構鏇願鏇積顧(糧襯襯鑰壓齋選觸衊膚) = 艱艱網淵願繭選鹽觸醖 積廠遞鏇選廠壓衊餘簾 (餘願憲鑰獵網窪艱艱鬱 ) | |||||||
临床4期 | 44 | Placebo | 廠夢窪齋糧遞顧襯網餘(鑰網鏇獵餘鑰窪餘餘鬱) = 鏇鹹築簾製顧壓築襯鬱 網餘鑰艱廠憲構衊蓋齋 (醖築憲顧齋觸遞蓋齋醖, 艱構廠遞襯蓋築齋製鹽 ~ 願選顧醖衊夢廠鹹膚鏇) 更多 | - | 2013-07-30 |
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