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zolpidem tartrate (Intermezzo / zolpidem, TransOral)

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Transcept Pharmaceuticals · GABRA1 · 小分子

什么是 zolpidem tartrate？

zolpidem tartrate 是一种小分子，由Transcept Pharmaceuticals研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)、Sublingual (SL)/Oral Transmucosal。

药物档案

商品名Intermezzo, zolpidem, TransOral
公司Transcept Pharmaceuticals
药物类别小分子
分子靶点GABRA1
给药途径Oral (PO), Sublingual (SL)/Oral Transmucosal
状态Approved
来源： ClinicalTrials.gov, Transcept Pharmaceuticals

作用机制

分子靶点

zolpidem tartrate 作用于 1 个分子靶点：

GABRA1gamma-aminobutyric acid type A receptor alpha1 subunit (DEE19, ECA4)
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

zolpidem tartrate 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
Psychiatric disordersInsomnia✓ Approved

相关研究文献

PubMedDentistry journal2026-07-27

Estradiol Enhances Alveolar Bone Resorption by Promoting Osteoclast Differentiation in Experimental Periodontitis.

Yasuda Keisuke K, Matsuda Shinji S, Memida Takumi T, Yoshimoto Tetsuya T et al.

Background/Objectives: Estrogen is a key female hormone; however, its role in periodontitis remains poorly understood. This study investigated the effects of 17β-estradiol (E2) on experimental periodontitis using an ovariectomy (OVX) model with E2 administration. Methods: Female mice aged 8-10 weeks underwent OVX, followed by induction of ligature-induced periodontitis, and subsequent quantification of alveolar bone resorption. Additional groups received an aromatase inhibitor or E2 supplementation after OVX, with subsequent induction of periodontitis and evaluation of bone resorption. Histological analysis assessed multinucleated giant cells and tartrate-resistant acid phosphatase-positive osteoclasts on the bone surface. Gingival tissue was analyzed for gene expression related to osteoclastogenesis. The effect of E2 on osteoclast differentiation from bone marrow cells was also examined. Results: OVX significantly reduced serum E2 levels and decreased alveolar bone resorption. Aromatase inhibitor administration similarly reduced bone loss. Histological evaluation revealed a reduced number of resorbing osteoclasts in OVX mice, whereas E2 supplementation increased osteoclast numbers. No significant changes in inflammatory cytokine or receptor activator of nuclear factor-kappa B ligand (RANKL) expression were observed. E2 promoted osteoclast differentiation in vitro, and treatment with E2 prior to RANKL stimulation further increased the number of osteoclasts. This effect was suppressed by an estrogen receptor antagonist. Moreover, E2 enhanced the expression of osteoclast differentiation-associated genes in the presence of RANKL, an effect abolished by tamoxifen. Conclusions: E2 increased alveolar bone resorption in experimental periodontitis, likely by promoting osteoclast differentiation, independent of inflammatory cytokine or RANKL gene expression.

PMID 42505728
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PubMediScience2026-07-26

Skipjack tuna bone-derived biocalcium ameliorates osteoblast and osteoclast differentiation through microRNA21 regulation.

Jantarawong Sompot S, Phuntong Sudarat S, Kanobthammakul Saowapak S, Watcharanurak Papitchaya P et al.

Alternative calcium sources are needed to enhance osteoporosis management. This study investigated the osteoprotective effects of skipjack tuna bone-derived biocalcium (Bio). Bio enhanced MC3T3-E1 osteoblast and C3H10T1/2 cell differentiation, increasing alkaline phosphatase activity and calcium deposition. Conversely, Bio inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in RAW 264.7 macrophages, reducing tartrate-resistant acid phosphatase (TRAP) activity and bone resorption. Bio suppressed intracellular ROS and downregulated primary, precursor and mature microRNA (miR)-21. miR-21 inhibitor suppressed TRAP activity and Cathepsin K expression, as opposed to miR-21 mimic. In an osteoblast-osteoclast crosstalk environment, Bio synergistically enhanced miR-21 target genes (PTEN and PDCD4) expression, whereas PTEN knockdown suppressed NFATc1 osteoclast marker expression via miR-21 inhibition. Molecular docking confirmed binding affinities between mouse and human miR-21 and both targets. Western blot showed β-catenin upregulation and total NF-κB p65 suppression after Bio treatment. Collectively, Bio exerts dual anti-osteoporotic actions, offering a potential functional supplement for bone remodeling disorders.

PMID 42502385
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PubMedArchives of oral biology2026-07-26

Remodeling of the sagittal suture development in sclerostin knockout male mice associated with cranial flat bone growth.

Chao Fan-Yi FY, Shimoe Saiji S, Mine Yuichi Y, Taji Tsuyoshi T et al.

The purpose of this study was to examine the effect of lack of sclerostin gene (Sost) on the growth and development of cranial bone associated with sagittal suture. 10, 15, 30, and 60-day-old wild-type mice and Sost knockout (SostΔ26/Δ26) mice were served in this study. The calvariae including sagittal sutures were removed and observed microscopically. The activity of osteoclast was examined by tartrate-resistant acid phosphatase (TRAP) staining and the expression of sclerostin and β-catenin were evaluated by immunohistochemical methods. It was shown that SostΔ26/Δ26 mice resulted in increased bone formation, leading to thickening of the calvaria. Suture stenosis and partial bone obliteration accompanied by higher expressive levels of β-catenin have also been observed in SostΔ26/Δ26 mice, while sagittal suture remains its patency in the late developmental stage. These results suggest that SostΔ26/Δ26 mice shows accumulation of β-catenin, inducing a metabolic effect on bone remodeling during the early postnatal period, which may be related to the abnormality of cranial suture in SostΔ26/Δ26 mice.

PMID 42501485
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PubMedJournal of biomedical materials research. Part A2026-07-24

Effect of Osteoblast-Extracellular Matrix-Functionalized Nanostructured Titanium Surface on Osteoblastic Cell Behavior.

Quiles Georgia Kors GK, Souza Paola Gomes PG, Gomes Maria Paula Oliveira MPO, Bighetti-Trevisan Rayana Longo RL et al.

Nanostructured titanium (Ti) facilitates osteoblast differentiation by modulating various signaling pathways and may enhance osseointegration, potentially through its influence on the formation and remodeling of the extracellular matrix (ECM). This study aimed to investigate the impact of osteoblast-ECM-functionalized nanostructured Ti surface on osteoblastic cell behavior. Initially, it was demonstrated that nanotopography upregulated the expression of genes associated with ECM formation and remodeling in MC3T3-E1 osteoblastic cells compared to a polished Ti surface. Then, MC3T3-E1 cells were cultured on nanotopography, and the cultures were decellularized to generate ECM-functionalized nanostructured Ti surface. Successful decellularization was verified by 4',6-diamidino-2-phenylindole staining for DNA, DNA quantification, fibronectin immunodetection and scanning electron microscopy. To investigate the effect of ECM functionalization on osteoblasts, calvaria-derived osteoblasts were cultured on both non-functionalized and osteoblast-ECM-functionalized nanostructured Ti surfaces. ECM functionalization did not affect cell morphology but reduced proliferation and the gene expression of osteoblastic markers while increasing alkaline phosphatase activity and ECM mineralization. Additionally, RAW 264.7 osteoclastic cells cultured on ECM-functionalized surface exhibited higher tartrate-resistant acid phosphatase activity. Functionalization of nanostructured Ti surfaces created a favorable microenvironment for bone cell activity and bone remodeling, contributing to the development of smart osseointegrated Ti implants.

PMID 42494283
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PubMedClinical and translational science2026-07-24

Metoprolol Population Pharmacokinetics in Older Chinese Patients With CKM Syndrome: Joint Effects of rs1065852 and CKM2S2-BAG Score on Clearance.

Chai Haodi H, Sia Jie En Valerie JEV, Hu Dingyuan D, Jia Yunshu Y et al.

Older adults are vulnerable to adverse drug reactions due to multimorbidity, frailty and polypharmacy. In those with cardiovascular-kidney-metabolic (CKM) syndrome, CKM-related multi-organ burden may further alter drug disposition and elevate risk. Metoprolol exposure varies widely among individuals, and higher plasma concentrations have been associated with falls in prior studies. We aimed to develop a population pharmacokinetic (PopPK) model of metoprolol in older Chinese patients with CKM syndrome using real-world data, identify key covariates affecting clearance, and perform model-based dose simulations. The PopPK analysis included sparse real-world data from 42 older adults (60-93 years) receiving immediate-release metoprolol tartrate. Candidate covariates included demographics, genetic polymorphism, laboratory variables, comorbidities, frailty phenotype, SARC-F score, age-adjusted Charlson Comorbidity Index, CKM stage and CKM2S2-BAG score. Model-based simulations were conducted across predefined genotype- and disease-burden strata to evaluate dosing scenarios against literature-based thresholds. Metoprolol pharmacokinetics were adequately described by a one-compartment model with first-order absorption and elimination. The rs1065852 T/T genotype and a high CKM2S2-BAG score (> 11) were associated with lower apparent clearance (CL/F), resulting in approximately 32% and 30% reductions in CL/F, respectively, and reduced interindividual variability in CL/F from 46.9% to 39.9%. Simulations identified subgroup-specific dosing regimens that maintained steady-state trough concentrations within a literature-derived range. In older Chinese patients with CKM syndrome, rs1065852 and CKM-related burden influenced metoprolol clearance and accounted for a considerable part of the observed variability between individuals. This study provides a model-informed framework for exposure-threshold-based dose stratification. Prospective validation with clinical outcomes and comprehensive CYP2D6 genotyping is warranted.

PMID 42496093
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PubMedAutophagy2026-07-24

Targeting NAE1 suppresses osteoclastogenesis via dual regulation of ferritinophagy and ACSL3-mediated ferroptosis.

Xie Hongwei H, Xie Jiachen J, Dai Zihan Z, Zhang Jiateng J et al.

Neddylation regulates diverse cellular processes, yet its role in osteoclast-mediated bone resorption is poorly understood. Here, we identify NAE1 (NEDD8 activating enzyme E1 subunit 1)-mediated neddylation as a critical regulator of postmenopausal osteoporosis and osteoclast differentiation through two distinct regulatory mechanisms. Pharmacological inhibition of Nae1 or myeloid-specific genetic ablation of Nae1 attenuated osteoclastogenesis in vitro and ameliorated ovariectomy (OVX)-induced osteoporosis in vivo without impairing osteoblast function. Mechanistically, Nae1 depletion disrupted intracellular iron metabolism, thereby suppressing ferritinophagy initiation in osteoclast precursors. Concurrently, integrated transcriptomics and affinity purification-mass spectrometry revealed ACSL3 as a direct neddylation substrate. Nae1-mediated neddylation modulates monounsaturated fatty acid (MUFA) biosynthesis, regulating the sensitivity of bone marrow-derived macrophages (BMDMs) to ferroptosis. This dual regulatory mechanism coordinately governs ferritinophagy initiation in iron metabolism and the sensitivity to ferroptosis mediated by ACSL3 neddylation, thereby critically influencing osteoclastogenesis. Clinically, serum MUFA levels positively correlated with bone mineral density (r = 0.329, p < 0.05). These findings support MLN4924, a clinical-stage NAE inhibitor, as a potential therapeutic strategy for osteoporosis and define an Nae1-ACSL3-MUFA-ferroptosis axis regulating osteoclast metabolism.Abbreviations: 4-HNE: 4-hydroxynonenal; ACP5/TRAP: acid phosphatase, tartrate resistant; ACSL3: acyl-CoA synthetase long chain family member 3; ACSL4: acyl-CoA synthetase long chain family member 4; BGLAP/OCN: bone gamma-carboxyglutamate protein; BMD: bone mineral density; BMDMs: bone marrow-derived macrophages; BV/TV: bone volume per total volume; CHX: cycloheximide; cKO: conditional knockout; co-IP: co-immunoprecipitation; CTSK: cathepsin K; DFO: deferoxamine; MDS: myelodysplastic syndrome; MUFA: monounsaturated fatty acid; NAE1: NEDD8 activating enzyme E1 subunit 1; NCOA4: nuclear receptor coactivator 4; NEDD8: NEDD8 ubiquitin like modifier; NFE2L2: NFE2 like bZIP transcription factor 2; NFATC1: nuclear factor of activated T cells 1; OC: osteoclast; OVX: ovariectomy; PUFA: polyunsaturated fatty acid; ROS: reactive oxygen species; RUNX2: RUNX family transcription factor 2; SLC40A1: solute carrier family 40 member 1; SLC7A11: solute carrier family 7 member 11; Tb.N: trabecular number; Tb.Sp: trabecular separation; Tb.Th: trabecular thickness; TFRC: transferrin receptor; TNFSF11/RANKL: TNF superfamily member 11; UBE2M: ubiquitin conjugating enzyme E2 M.

PMID 42495964
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