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

Norepinephrine reuptake inhibitors, Serotonin reuptake inhibitors

Therapeutic Areas

Immune System DiseasesNervous System DiseasesCongenital Disorders+ [2]

Active Indication

Sleep Initiation and Maintenance DisordersDermatitis, AtopicNeurodermatitis+ [3]

Inactive Indication-

Originator Organization

Pfizer Laboratories (Pty) Ltd.

Active Organization

Endo International PlcMylan Pharmaceuticals, Inc.

Hunan Jianlang Pharmaceutical Co. Ltd.

+ [4]

Inactive Organization

Pfizer Laboratories (Pty) Ltd.

Drug Highest PhaseApproved

First Approval Date

US (23 Sep 1969),

AnxietyDepressive Disorder

Regulation-

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Structure

Molecular FormulaC19H22ClNO

InChIKeyMHNSPTUQQIYJOT-UHFFFAOYSA-N

CAS Registry1229-29-4

Rationale: Nonbenzodiazepine benzodiazepine receptor agonists (NBZRA, e.g., zolpidem) are frequently used to treat insomnia among patients with chronic obstructive pulmonary disease (COPD). However, multiple observational studies find that patients with COPD who are prescribed NBZRAs have greater risks for mortality and respiratory complications than patients without such prescriptions. Without an active comparator, these studies are susceptible to confounding by indication. Objectives: Compare the risk of death or inpatient COPD exacerbation among patients receiving zolpidem relative to patients receiving other hypnotics. Methods: Using nationwide Veterans Health Administration (VA) data, we identified patients with clinically diagnosed COPD and new receipt of zolpidem or another hypnotic available on VA formulary without prior authorization (melatonin, trazodone, doxepin). We excluded those receiving traditional benzodiazepines or multiple concurrent hypnotics. We propensity-matched patients receiving zolpidem to other hypnotics on 32 variables, including demographics, comorbidities, and markers of COPD severity. We compared risk of the primary composite outcome of death or inpatient COPD exacerbation over 1 year. In secondary analyses, we propensity-matched patients receiving zolpidem to those without hypnotic receipt. Results: Among 283,740 patients meeting inclusion criteria, 1,126 (0.4%) received zolpidem and 3,057 (1.1%) received other hypnotics. We propensity-matched patients receiving zolpidem 1:1 to peers receiving other hypnotics. We did not find a difference in the primary composite outcome of death or inpatient exacerbation (hazard ratio, 0.97; 95% confidence interval [CI], 0.77-1.23). In secondary analyses comparing patients receiving zolpidem to matched peers without hypnotic receipt, we observed greater risk of death or inpatient exacerbation with zolpidem (hazard ratio, 1.40; 95% CI, 1.09-1.81). Conclusions: Among patients with COPD, we did not observe greater risks after new receipt of zolpidem relative to other hypnotics. However, we did observe greater risks relative to those without hypnotic receipt. This latter finding may reflect: 1) residual, unmeasured confounding related to insomnia; or 2) true adverse effects of hypnotics across classes. Future work is needed to better understand the risks of hypnotics in COPD.

04 Dec 2023·Molecular pharmaceutics

Stereoselective Inhibition of High- and Low-Affinity Organic Cation Transporters

Article

Author: Rafehi, Muhammad ; Brockmöller, Jürgen ; Jensen, Ole ; Gebauer, Lukas

Many drugs have chiral centers and are therapeutically applied as racemates. Thus, the stereoselectivity in their interactions with membrane transporters needs to be addressed. Here, we studied stereoselectivity in inhibiting organic cation transporters (OCTs) 1, 2, and 3 and the high-affinity monoamine transporters (MATs) NET and SERT. Selectivity by the inhibition of 35 pairs of enantiomers significantly varied among the three closely related OCTs. OCT1 inhibition was nonselective in almost all cases, whereas OCT2 was stereoselectively inhibited by 45% of the analyzed drugs. However, the stereoselectivity of the OCT2 was only moderate with the highest selectivity observed for pramipexole. The (R)-enantiomer inhibited OCT2 4-fold more than the (S)-enantiomer. OCT3 showed the greatest stereoselectivity in its inhibition. (R)-Tolterodine and (S)-zolmitriptan inhibited OCT3 11-fold and 25-fold more than their respective counterparts. Interestingly, in most cases, the pharmacodynamically active enantiomer was also the stronger OCT inhibitor. In addition, stereoselectivity in the OCT inhibition appeared not to depend on the transported substrate. For high-affinity MATs, our data confirmed the stereoselective inhibition of NET and SERT by several antidepressants. However, the stereoselectivity measured here was generally lower than that reported in the literature. Unexpectedly, the high-affinity MATs were not significantly more stereoselectively inhibited than the polyspecific OCTs. Combining our in vitro OCT inhibition data with available stereoselective pharmacokinetic analyses revealed different risks of drug-drug interactions, especially at OCT2. For the tricyclic antidepressant doxepine, only the (E)-isomer showed an increased risk of drug-drug interactions according to guidelines from regulatory authorities for renal transporters. However, most chiral drugs show only minor stereoselectivity in the inhibition of OCTs in vitro, which is unlikely to translate into clinical consequences.

01 Nov 2023·International journal of pharmaceutics

Utilizing a microfluidic platform to investigate drug-eluting beads: Binding and release of amphiphilic antidepressants

Article

Author: Wanselius, Marcus ; Hansson, Per ; Al-Tikriti, Yassir

Drug-eluting beads made of responsive polyelectrolyte networks are used in the treatment of liver cancer. Aggregates of loaded drugs in complex with the networks dissolve upon release, causing swelling of the network. According to a recent mechanism the release and swelling rates are controlled by the mass transport of drug through a depletion layer created in the microgel. We hypothesise that the mechanism, in which the stability of the drug aggregates and the swelling properties of the network play crucial roles, offers means to control the release profile also for other drugs. To test this, we investigated the loading and release properties of amitriptyline, chlorpromazine and doxepin in polyacrylate, hyaluronate and DCbead™ microgels in a microfluidic setup. Loaded drugs could be released to a medium with physiological ionic strength and pH. The binding strength increased with decreasing critical micelle concentration of the drugs and increasing linear charge density of network chains. Microgels displayed drug-rich core/swollen shell coexistence, and swelled during release at a rate in agreement with the depletion layer mechanism, indicating its generality. The results demonstrate the potential of microgels as vehicles for amphiphilic drugs and the usefulness of the microfluidics method for in vitro studies of such systems.

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

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	US	Pfizer Laboratories (Pty) Ltd.	23 Sep 1969
Depressive Disorder	US	Pfizer Laboratories (Pty) Ltd.	23 Sep 1969

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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	leikgyunmt(cowwqhuasg) = qcxnwcsebm gctrubzwna (gapphpbuge, uuigsuagvm - llbeddjnmk) View more	-	01 Oct 2019
NCT02229539 (Alliance A221304, Pubmed \| J Coll Physicians Surg Pak)	Phase 3	radiation oral mucositis	275	Doxepin Mouthwash	lxgitbjbmh(pzhxmtvzcz) = osxcpmtujz rrembzpmrx (immhxlrwqc ) View more	Positive	16 Apr 2019
NCT01156142 (CTgov)	Phase 3	Stomatitis \| Pain \| Head and Neck Neoplasms ... View more	155	Placebo+Doxepin (Arm I (Doxepin-Placebo))	ndjnywmfzm(nqpjrggpoa) = icghlouutg gfprikzbas (fswjwgejhl, qzfhlshjbj - krxuiromnt) View more	-	08 May 2017
NCT01156142 (CTgov)	Phase 3	Stomatitis \| Pain \| Head and Neck Neoplasms ... View more	155	Placebo+Doxepin (Arm II (Placebo-Doxepin))	ndjnywmfzm(nqpjrggpoa) = emoityyhxv gfprikzbas (fswjwgejhl, sniimlljve - smbxkpycxl) View more	-	08 May 2017
NCT02229539 (CTgov)	Phase 3	Stomatitis	275	Doxepin (Doxepin)	cbzafljdfp(rogflcftam) = strjydfmqw hvdcpqmznm (draucfyurw, tjrrsdyifa - fdfiolegrj) View more	-	10 Apr 2017
NCT02229539 (CTgov)	Phase 3	Stomatitis	275	DLA+Lidocaine+Diphenhydramine (DLA (Diphenhydramine, Lidocaine and Antacid))	cbzafljdfp(rogflcftam) = uvztfkglzb hvdcpqmznm (draucfyurw, bqxnrdbiov - oduwmymxcu) View more	-	10 Apr 2017
NCT00465972 (CTgov)	Phase 4	Sleep Initiation and Maintenance Disorders \| HIV Infections	44	Placebo	pxgzhacarb(rlkwivsjft) = igxlzrfpiy yeufqqjxgi (pinyjyprht, qymehrqzym - nlghcmsfwg) View more	-	30 Jul 2013