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doxepin (doxepin, GenDerm / Zonalon / Xepicort)

✓ Approved

Takeda · HRH1 · 小分子

什么是 doxepin？

doxepin 是一种小分子，由Takeda研发。该药已获批，用于治疗相关适应症，给药途径：Topical。

药物档案

商品名doxepin, GenDerm, Zonalon, Xepicort
公司Takeda
药物类别小分子
分子靶点HRH1, HRH2, SLC6A2
给药途径Topical
状态Approved
来源： ClinicalTrials.gov, Takeda

作用机制

分子靶点

doxepin 作用于 3 个分子靶点：

HRH1histamine receptor H1 (HH1R, H1R)
HRH2histamine receptor H2 (HH2R, H2R)
SLC6A2solute carrier family 6 member 2 (SLC6A5, NAT1)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

doxepin 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Skin and subcutaneous tissue disordersPruritus✓ Approved

相关研究文献

PubMedJournal of psychopharmacology (Oxford, England)2026-08-04

A pharmacometric framework for norepinephrine transporter occupancy and dose equivalence across psychotropic medications.

Aboukaoud Mohammed M, Hoch Bosmat B, Amiaz Revital R

Norepinephrine transporter (NET) inhibition is a relevant mechanism across psychotropic medications, although prescribing classifications are largely based on drug class rather than quantitative target engagement. To facilitate cross-drug comparisons of noradrenergic activity, we developed a pharmacometric model to estimate NET occupancy for 26 psychotropic agents and their active metabolites. NET occupancy was estimated using National Institute of Mental Health Psychoactive Drug Screening Program Ki data, protein-binding-corrected plasma concentrations, a standard receptor occupancy model, and logit-derived ED50 values, and was compared with published positron emission tomography (PET) estimates. After protein-binding correction, desipramine, milnacipran, and maprotiline showed very high NET occupancy (⩾90%), nortriptyline, doxepin, and norquetiapine showed high occupancy (70%-90%), and hydroxybupropion and duloxetine showed moderate occupancy (50%-70%). Clomipramine, atomoxetine, and reboxetine demonstrated moderate-low occupancy (30%-50%), whereas venlafaxine showed low occupancy (~28%). Hydroxybupropion exhibited substantially greater NET engagement (~68%) than bupropion (~2%), and most Selective serotonin reuptake inhibitors showed minimal occupancy (<10%). Estimated ED50 values ranged from 6.6 mg (desipramine) to ⩾63 mg (duloxetine), and predicted occupancies correlated moderately with PET data (r = 0.76, p = 0.028, R² = 0.58). These findings suggest that variability in NET engagement across psychotropic medications may not be fully captured by conventional class-based classifications. The proposed framework offers a mechanism-informed approach to comparative pharmacological analysis and introduces a conceptual noradrenergic activity index. This approach may be useful for hypothesis generation in future studies integrating pharmacokinetic-pharmacodynamic modeling with in vivo imaging and clinical outcomes.

PMID 42549822
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PubMedZhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases2026-07-31

[Determination of doxepin and nordoxepin in plasma by solid-phase extraction coupled with liquid chromatography-mass spectrometry (PRiME MCX-UPLC-HRMS)].

Chen X D XD, Wang Q Q QQ, Cai J J JJ, Pan S D SD

Objective: To establish a rapid method for the determination of doxepin and its metabolite nordoxepin residues in plasma samples by PRiME mixed cation-exchange solid-phase extraction coupled with ultra-performance liquid chromatography-high resolution mass spectrometry (PRiME MCX-UPLC-HRMS) . Methods: Plasma samples were extracted with 2% (V/V) aqueous phosphoric acid and purified by a PRiME MCX SPE cartridge. The target compounds were separated on an aurorasil MMP-G column (100 mm×2.1 mm, 3 μm) and gradient elution was performed with the mobile phases 5.0 mmol/L ammonium formate -0.1% (V/V) aqueous formic acid and methanol, and were determined in electrospray positive ionization mode (ESI(+)) and full mass scan-data dependent ms(2) scan (Full mass-ddMS(2)) mode, and the internal standard method was used for quantification. The limits of detection (LODs) and limits of quantification (LOQs) were calculated at signal-to-noise ratios of 3 and 10, respectively. Results: The linear ranges of doxepin and its metabolite nordoxepin were 1.0-100.0 ng/ml with correlation coefficients of 0.9988-0.9999. The LODs and LOQs for doxepin and its metabolite nordoxepin were determined to be 0.18-0.22 ng/ml and 0.54-0.66 ng/ml, respectively. The spiked recoveries of doxepin and its metabolite nordoxepin in plasma at the four concentration levels of 1.0 ng/ml, 10.0 ng/ml, 50.0 ng/ml and 80 ng/ml ranged from 90.8% to 105%, with relative standard deviations (RSDs) of 1.31%-4.59%. Conclusion: The method was rapid, sensitive and accurate and was suitable for the monitoring and analysis of doxepin and its metabolite nordoxepin in plasma samples from clinical patients.

PMID 42533659
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PubMedMicrobial pathogenesis2026-07-28

Antifungal and anti-biofilm activity of doxepin against Candida spp. mediated by oxidative stress and modulation of adhesion-related genes.

Pinheiro Dávylla Rênnia Saldanha DRS, Barbosa Sarah Alves SA, de Oliveira Leilson Carvalho LC, de Farias Cabral Vitória Pessoa VP et al.

Candida species are associated with invasive infections characterized by causing high rates of mortality and morbidity, particularly when linked to biofilm formation. The present study investigated the in vitro antifungal activity of doxepin (DOX) against fluconazole-resistant strains of Candida spp., including 10 clinical isolates, 2 ATCC strains and 1 CDC strain. Antifungal susceptibility assays were performed on planktonic cells and biofilms, followed by cytometric analyses, including reactive oxygen species (ROS) production, mitochondrial depolarization, phosphatidylserine externalization, and cell viability. Molecular analyses involved docking and gene expression by qRT-PCR. DOX exhibited fungicidal activity against all strains, with MIC50 values ranging from 64 to 256 μg/mL, as well as significant reduction of biofilm formation. In combination with amphotericin B, a predominantly synergistic effect was observed, with increased efficacy at lower concentrations. Mechanistically, DOX induced oxidative stress, mitochondrial dysfunction, and apoptosis, reducing fungal viability. The in silico ADME profile showed high gastrointestinal absorption, indicating potential for oral bioavailability, compatible with systemic use. Furthermore, it established stable interactions with the Als3 and Sap5 proteins, also promoting changes in the expression of virulence-related genes, such as als3, sap5, ece1, and hwp1. These findings indicate that DOX exhibits promising antifungal activity for the treatment of Candida infections, particularly highlighting its potential against biofilms.

PMID 42508701
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PubMedObesity surgery2026-07-15

Prevalence of Psychotropic Drug Treatment Interventions in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Study.

Wever Susannah Anna-Maria Leilani SAL, Sizoo Dionne D, van Roon Eric Nico EN, Cheung Victoria Hiu Yeung VHY et al.

The pharmacokinetics of oral psychotropic drugs can change after metabolic and bariatric surgery (MBS), affecting drug exposure. Given the risk of psychiatric decompensation, patients using psychotropic medications constitute a high-risk group requiring careful post-MBS monitoring. In particular, lithium, tricyclic antidepressants (TCAs), and clozapine are of concern because of their well-established dose-effect relationships, susceptibility to MBS-related exposure changes, and suitability for therapeutic drug monitoring (TDM). This study aimed to examine the prevalence of treatment interventions related to these medications in bariatric patients to prevent drug-related problems such as under- or overexposure requiring dosage adjustments or drug discontinuation. In this retrospective study, patient records from January 2017 to December 2023 were reviewed. Patients who underwent MBS and were using lithium, TCAs (amitriptyline, clomipramine, dosulepin, doxepin, imipramine, maprotiline, nortriptyline), and/or clozapine were included. Baseline characteristics, treatment interventions, and available drug plasma concentrations were collected preoperatively and up to one year postoperatively. A total of 163 patients were included. Psychotropic drug adjustments were observed in 27 patients (16.6%) within the first year following MBS. Both pre- and postoperative drug plasma concentrations were available for three patients (1.8%). Three patients experienced worsening of psychiatric symptoms that necessitated hospitalization or intensive monitoring. No statistically significant differences in intervention rates were observed among patients with psychiatric disorders or pain. Although only a minority of patients required psychotropic drug treatment interventions, monitoring psychotropic drug treatment is essential for safe and effective treatment post-MBS. Greater attention is needed regarding altered drug exposure, and plasma concentration monitoring may help optimize psychotropic pharmacotherapy in these patients.

PMID 42455492
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PubMedMolecular neurodegeneration2026-05-23

Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice.

Sharma Ashish A, Segawa Emiko E, Chen Xiaoying X, Park Sohui S et al.

Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer's disease (AD). The orexin/hypocretin system regulates sleep-wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice. PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed by piezoelectric monitoring and EEG/EMG polysomnography. Amyloid pathology and microglial responses were quantified by immunohistochemistry, confocal microscopy, and single-cell RNA sequencing. Microglial depletion was induced with the CSF1R inhibitor PLX3397. Lemborexant enhanced sleep quality with less active-phase sedation than doxepin. Both drugs reduced initial diffuse plaque deposition, but only lemborexant prevented fibrillar plaque accumulation in young mice and slowed plaque growth in older mice. Lemborexant increased peri-plaque microglial CD68 expression and enhanced Aβ phagocytosis in vivo. Single-cell transcriptomics revealed a shift toward activated, DAM-like microglial states with upregulation of phagocytic genes without broad inflammatory induction. Microglial depletion abolished lemborexant's anti-amyloid effects. Lemborexant mitigates amyloid pathology by augmenting microglial phagocytic function, positioning DORAs as promising therapeutics that couple sleep promotion with beneficial microglial modulation.

PMID 42174655
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PubMedPrimary care2026-05-13

Pharmacologic Management of Insomnia in Adults.

Williamson Brandon B

Insomnia is a common reason for patients to seek medical care. A careful history should be obtained to identify predisposing, precipitating, and perpetuating factors contributing to sleep disturbance. Cognitive behavioral therapy for insomnia is the first-line treatment for chronic insomnia, offering effectiveness with minimal risk, though access may be limited by availability. Pharmacologic therapy should ideally be reserved for short-term use and initiated only after setting clear expectations and considering potential risks. Evidence-based medication options include low-dose doxepin, melatonin receptor agonists, dual orexin receptor antagonists, and nonbenzodiazepine benzodiazepine receptor agonists. Ongoing follow-up is essential to monitor treatment response.

PMID 42120158
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