Delving into the Latest Updates on Doxepin hydrochloride with Synapse

Overview

Basic Info

SummaryDoxepin, the small molecule drug, serves as a cogent therapeutic agent, targeting both the norepinephrine transporter (NET) and serotonin transporter subtype 5 (SERT-5). Through the dual action of inhibiting the reuptake of both norepinephrine and serotonin in the brain, doxepin functions as a resplendent antidepressant, leading to an escalation in the levels of these neurotransmitters within the synaptic cleft. This neurochemical alteration helps to stabilize mood, mitigate anxiety, and augment sleep quality, thereby yielding numerous benefits. From its inception, in September 1969, doxepin has been the beacon of hope for those struggling with depression, anxiety disorders, and insomnia. Nonetheless, it is imperative to be cognizant of the fact that doxepin can induce some untoward effects, including, but not limited to, drowsiness, dry mouth, constipation, and weight gain, and may even interact with other medications. Therefore, it is judicious to utilize doxepin with due caution under the discerning guidance of a healthcare professional.

Drug Type

Small molecule drug

Synonyms

Doxepin, Doxepin hydrochloride (USP), Doxepin Hydrochloride Cream

+ [16]

Target

NET x SERT

Mechanism

NET inhibitors(Norepinephrine transporter inhibitors), Serotonin reuptake inhibitors

Therapeutic Areas

Immune System DiseasesNervous System DiseasesCongenital Disorders+ [3]

Active Indication

Sleep Initiation and Maintenance DisordersDermatitis, AtopicNeurodermatitis+ [4]

Inactive Indication

Esophageal CarcinomaEsophagitisHead and Neck Neoplasms+ [15]

Originator Organization

Pfizer Laboratories (Pty) Ltd.

Active Organization

Endo International Plc

Taicang Pharmaceutical FactoryMylan Pharmaceuticals, Inc.

+ [5]

Inactive Organization

National Cancer InstitutePfizer Laboratories (Pty) Ltd.

Drug Highest PhaseApproved

First Approval Date

US (23 Sep 1969),

Anxiety DisordersDepressive Disorder

Regulation-

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Structure

Molecular FormulaC19H22ClNO

InChIKeyMHNSPTUQQIYJOT-UHFFFAOYSA-N

CAS Registry1229-29-4

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.

01 Sep 2024·CLINICAL TOXICOLOGY

Evolving trends of pharmaceutical poisonings associated with QRS complex prolongation

Article

Author: 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.

01 Sep 2024·JOURNAL 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

Author: 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.

2

News (Medical) associated with Doxepin hydrochloride

26 Oct 2021

·www.biospace.com

Currax Pharmaceuticals Announces the Appointment of Ed Cinca to Senior Vice President, Global Marketing and Strategic Alliance Management

Appointment comes during period of accelerated growth for Currax and its lead asset, CONTRAVE®, the number one prescribed oral weight-loss brand medication in the US [26-October-2021] BRENTWOOD, Tenn., Oct. 26, 2021 /PRNewswire/ -- Currax Pharmaceuticals, LLC ("Currax"), a specialty biopharmaceutical company dedicated to expanding access to clinical differentiated medicines – both branded and generic – today announced the appointment of Ed Cinca to the role of Senior Vice President (SVP), Global Marketing and Strategic Alliance Management, reporting to Currax's President and Chief Executive Officer, George Hampton. As the SVP, Global Marketing and Strategic Alliance Management, Ed's role will be to lead worldwide commercial strategy for the entire Currax portfolio with a priority focus on CONTRAVE® (naltrexone HCl/bupropion HCl), the number one prescribed oral weight-loss brand medication in the US. Ed will also oversee the Company's global partnerships and strategic alliances. "Obesity is the number one preventable cause of death in the US and has accelerated in prevalence as a result of the pandemic. More must be done to help patients suffering from this disease," said Currax's President and CEO, George Hampton. "Currax is committed to this challenge and having Ed join our executive team increases our ability to support patients with obesity. His expertise in the category is unsurpassed and makes him a valuable addition to our leadership team." Prior to joining Currax, Ed most recently served as a Novo Nordisk, Inc. (NNI) Leadership Team Member and Vice President, Head of Cardiometabolic Portfolio, where he led the launches of Ozempic, Rybelsus and Wegovy. He previously held the roles of Vice President, Sales Execution and Operations, as well as Senior Brand Director of Saxenda® at NNI. Ed earned an MBA in Marketing and Finance from Fordham University and a Bachelor of Science in Finance from Lehigh University. He is also a board member of the New York/New Jersey American Diabetes Association and member of Steps Together, an organization that supports families impacted by medical crises. "Currax is an industry leader in the obesity space," said Ed Cinca. "I'm looking forward to applying my commercial experience in brand excellence and deep category expertise at such an exciting point in the Company's growth trajectory. I'm excited to help advance Currax's mission to enhance the lives of patients by providing access to life-changing medications that treat diseases such as obesity." Last month, Currax celebrated the official opening of its new headquarters location and the future of Currax's business in the Nashville area. About Currax Pharmaceuticals LLC: Currax Pharmaceuticals LLC is a specialty pharmaceutical business focused on acquiring and commercializing prescription Medicines worldwide. Currax distributes a range of both branded and generic pharmaceutical products, including CONTRAVE® (naltrexone HCl/bupropion HCl), ONZETRA® Xsail® (sumatriptan nasal powder), Silenor® (doxepin), Treximet®, (sumatriptan/naproxen sodium), and the authorized generic of Treximet®. For more information, please visit .

01 Nov 2012

·www.biospace.com

Somaxon Pharmaceuticals, Inc. Reports Third Quarter 2012 Financial Results

SAN DIEGO, Oct. 31, 2012 (GLOBE NEWSWIRE) -- Somaxon Pharmaceuticals, Inc. (Nasdaq:SOMX), a specialty pharmaceutical company, today reported its financial results for the third quarter ended September 30, 2012. "During the third quarter of 2012, we continued to focus on our key corporate objectives relating to Silenor commercialization and intellectual property protection, our financial position and our strategic alternatives process," said Richard W. Pascoe, Somaxon's President and Chief Executive Officer. "Commercially, we have continued to stabilize Silenor prescription volume quarter-over-quarter, and we have made solid progress in our managed care efforts, particularly with respect to the Medicare Part D market."

Financial Statement

100 Deals associated with Doxepin hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D00814	Doxepin hydrochloride	N06AA12 D04AX01	DB01142

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Sleep Initiation and Maintenance Disorders	US	Currax Pharmaceuticals LLCStartup	17 Mar 2010
Dermatitis, Atopic	US	Mylan Pharmaceuticals, Inc.	01 Apr 1994
Neurodermatitis	US	Mylan Pharmaceuticals, Inc.	01 Apr 1994
Pruritus	US	Mylan Pharmaceuticals, Inc.	01 Apr 1994
Anxiety Disorders	US	Pfizer Laboratories (Pty) Ltd.	23 Sep 1969
Depressive Disorder	US	Pfizer Laboratories (Pty) Ltd.	23 Sep 1969

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Head and Neck Neoplasms	Phase 3	US	National Cancer Institute	01 Dec 2010
Mucositis	Phase 3	US	National Cancer Institute	01 Dec 2010
Pain	Phase 3	US	National Cancer Institute	01 Dec 2010
Radiation Injuries	Phase 3	US	National Cancer Institute	01 Dec 2010
Stomatitis	Phase 3	US	National Cancer Institute	01 Dec 2010
Esophageal Carcinoma	Phase 2	US	National Cancer Institute	14 Apr 2014
Esophagitis	Phase 2	US	National Cancer Institute	14 Apr 2014
Hypopharyngeal Carcinoma	Phase 2	US	National Cancer Institute	14 Apr 2014
Laryngeal Neoplasms	Phase 2	US	National Cancer Institute	14 Apr 2014
Lymphoma	Phase 2	US	National Cancer Institute	14 Apr 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02062632 (CTgov)	Phase 2	Sarcoma \| Hypopharyngeal Carcinoma \| Neoplasm Metastasis ... View more	5	placebo	pgaihudjqj(pcpqxgfcsz) = yjedjcxwmz mpfduhbipa (amjjkgmcuk, fqekwkodne - qaexndixby) View more	-	01 Oct 2019
NCT01156142 (CTgov)	Phase 3	Pain \| Radiation Injuries \| Mucositis ... View more	155	Placebo+Doxepin (Arm I (Doxepin-Placebo))	jizpoamuqp(eyjnwvaoxh) = qnxbnyecut rctcvyvfsp (zejjdiolsh, wakhaqsptu - yzneiyyyaq) View more	-	08 May 2017
NCT01156142 (CTgov)	Phase 3	Pain \| Radiation Injuries \| Mucositis ... View more	155	Placebo+Doxepin (Arm II (Placebo-Doxepin))	jizpoamuqp(eyjnwvaoxh) = ufnrgndwjn rctcvyvfsp (zejjdiolsh, hcbryenpih - valtqjkwnp) View more	-	08 May 2017
A RANDOMIZED TRIPLE BLIND CONTROLLED TRIAL (UEGW)	Not Applicable	Irritable bowel syndrome with diarrhea	-	Doxepin 10mg	svpenhvjwq(dagbzuncvj) = eydjmcqarn qvjkwlbpnt (ulpclqnkto )	Positive	01 Oct 2016
A RANDOMIZED TRIPLE BLIND CONTROLLED TRIAL (UEGW)	Not Applicable	Irritable bowel syndrome with diarrhea	-	Nortriptyline 10mg	svpenhvjwq(dagbzuncvj) = dszdxprcnf qvjkwlbpnt (ulpclqnkto )	Positive	01 Oct 2016
NCT00465972 (CTgov)	Phase 4	Sleep Initiation and Maintenance Disorders \| HIV Infections	44	Placebo	wjkqsdngio(tcvhllfltf) = ueisqwjkgs jmrixcuwwp (jikjqkmszu, bxyqedofey - ukdjeboecp) View more	-	30 Jul 2013