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zolpidem tartrate (Intermezzo / zolpidem, TransOral)

✓ Approved

Transcept Pharmaceuticals · GABRA1 · Small Molecule

What is zolpidem tartrate?

zolpidem tartrate is a small molecule developed by Transcept Pharmaceuticals. It is approved for therapeutic indications via oral (po) or sublingual (sl)/oral transmucosal.

Drug Profile

Brand NamesIntermezzo, zolpidem, TransOral
CompanyTranscept Pharmaceuticals
Drug ClassSmall Molecule
Molecular TargetGABRA1
RouteOral (PO), Sublingual (SL)/Oral Transmucosal
StatusApproved
Sources: ClinicalTrials.gov, Transcept Pharmaceuticals

Mechanism of Action

Molecular Targets

zolpidem tartrate acts on 1 molecular target:

GABRA1gamma-aminobutyric acid type A receptor alpha1 subunit (DEE19, ECA4)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

zolpidem tartrate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersInsomnia✓ Approved

Related Research Articles

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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PubMedEuropean journal of nutrition2026-07-23

A 10-month cluster-randomized trial to shift towards plant-forward meals in early childhood education and care centres: effects on bone and mineral metabolism in Finnish children.

Itkonen Suvi T ST, Meinilä Jelena J, Niinistö Sari S, Raulio Susanna S et al.

A shift towards predominantly plant-based diets is emphasized for health and environmental sustainability, but it may affect nutrient adequacy and bone health. We investigated the effects of plant-forward meals in Finnish early childhood education and care (ECEC) centres on bone metabolism and intakes of bone nutrients in 3-5-year-old children. ECEC centres were cluster-randomized for 10 months into 11 intervention (more plant-based products and less red meat served and moderation in milk consumption encouraged; n = 55 children for individual-level study) and 12 control (maintained regular meals; n = 61 children) ECEC centres. In the intervention arm, 18 children and in the control arm 28 children provided complete (baseline and endpoint) blood samples and dietary data (food frequency questionnaire). Circulating biomarkers (e.g. serum tartrate-resistant acid phosphatase 5b [S-TRAP5b], total and bone-specific alkaline phosphatase [S-ALP; S-BAP], 25-hydroxyvitamin D [S-25(OH)D], and plasma parathyroid hormone) and intakes of calcium, vitamin D, phosphorus, and protein were analysed using mixed models. The intervention group had higher bone formation marker S-BAP (0.05 log-U/L, 95% CI 0.004-0.104; p = 0.04), bone resorption marker S-TRAP5b (2.12 U/L, 95% CI 0.35-3.90; p = 0.02), and S-ALP (0.034 log-U/L, 95% CI 0.002-0.066; p = 0.04) concentrations than the control group. No effects on other biomarkers or any nutrient intakes were observed. Mean S-25(OH)D concentrations were adequate (≥ 50 nmol/L). The clinical relevance of the results indicating accelerated bone turnover without observing any effects on the intakes of critical nutrients requires further investigations to avoid potential harmful consequences for long-term bone health with the shift to plant-forward diets. ClinicalTrials.gov, NCT05249946. Registered 29 November 2021, https://clinicaltrials.gov/ct2/show/NCT05249946 .

PMID 42489936
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PubMedJournal of nephrology2026-07-21

Association between bone turnover markers and bone mineral density after 12 months of exercise in patients with chronic kidney disease stages 3-5: a post-hoc exploratory sub-study of the RENEXC randomized controlled trial.

Petrauskiene Vaida V, Hellberg Matthias M, Svensson Philippa P, Clyne Naomi N

Chronic kidney disease (CKD) disrupts mineral and bone metabolism, increasing fracture risk. Exercise may improve physical performance and help preserve bone mineral density (BMD), but data on the relationship between BMD and bone turnover markers during long-term exercise in CKD are limited. We explored potential associations between intact procollagen type I N-propeptide (intact PINP), tartrate-resistant acid phosphatase 5b (TRAP5b) and BMD in CKD stages 3-5 patients completing 12 months of exercise. In this post-hoc, exploratory analysis of the RENEXC trial, 101 patients underwent 12 months of endurance exercise combined with strength or balance training. BMD was assessed by dual-energy X-ray absorptiometry, and plasma intact PINP and TRAP5b were measured at baseline and study end. Median intact PINP and TRAP5b remained largely unchanged. In adjusted analyses including clinical, medication-related, and CKD-MBD covariates, no consistent associations were observed between bone turnover markers and BMD. ΔBMD was not associated with changes in intact PINP or TRAP5b. In multivariate models, age was the only consistent predictor of osteoporotic status across time points, while associations with intact PINP and female sex were not stable after sensitivity analyses. In this cohort of patients with CKD stages 3-5 participating in a 12-month exercise intervention, circulating bone turnover markers (intact PINP and TRAP5b) showed minimal temporal change over 12 months and were not consistently associated with BMD or osteoporotic status after adjustment for clinical, biochemical, and treatment-related factors. Age was the only consistent variable associated with osteoporotic status across all models.

PMID 42479427
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PubMedPhytomedicine : international journal of phytotherapy and phytopharmacology2026-07-21

Cajaninstilbene Acid targets TNF-α-mediated mitochondrial translocation to restore osteogenic-osteoclastic coupling equilibrium and ameliorate estrogen-deficient osteoporosis.

Chen Benlu B, Lu Hongduo H, Gan Jiayu J, Hu Yunhao Y et al.

Oestrogen-deficient osteoporosis features an imbalanced bone formation-resorption coupling with excessive osteoclast activation and impaired osteoblast function. Compounds that bidirectionally regulate bone metabolism remain rare among natural small molecules. Cajaninstilbene acid (CSA) from Cajanus cajan leaves exerts regulatory effects on bone metabolism and anti-inflammatory activity, but its mechanism in restoring bone homeostasis via intercellular mitochondrial transfer remains unclear. To investigate the therapeutic effect of CSA on oestrogen-deficient osteoporosis and reveal its molecular mechanism by targeting TNF-α-mediated mitochondrial transfer to rebalance osteogenesis and osteoclastogenesis. Ovariectomised (OVX) mice were used as the estrogen-deficient osteoporosis model and treated with CSA for 6 weeks. Bone microstructure and metabolism were evaluated by micro-computed tomography (micro-CT), histological staining and immunohistochemistry (IHC). Primary bone marrow macrophages (BMMs) and bone marrow mesenchymal stem cells (BMSCs) were cultured for osteoclastic and osteogenic differentiation. Differentiation was assessed by tartrate-resistant acid phosphatase (TRAcP), alkaline phosphatase (ALP) and alizarin red staining (ARS). Key targets were screened by transcriptomic analysis and validated by molecular docking and surface plasmon resonance (SPR). Mitochondrial transfer and activity were observed by co-culture, fluorescence labelling and JC-1 staining. Protein and gene expression were determined by Western blot (WB) and quantitative real-time polymerase chain reaction (qPCR). CSA significantly increased bone mineral density and improved trabecular microarchitecture in OVX mice without obvious hepatorenal toxicity. In vitro, CSA dose-dependently suppressed RANKL-induced osteoclastogenesis by downregulating NFATc1 and CTSK, while enhancing osteoblast differentiation by upregulating RUNX2, OCN and OPG. Mechanistically, CSA directly bound and inhibited TNF-α, upregulated the mitochondrial transporter MIRO1, and restored mitochondrial transfer from osteoblasts to osteoclasts, reversing the disrupted bone coupling balance. CSA bidirectionally inhibits bone resorption and promotes bone formation by blocking TNF-α signalling and restoring MIRO1-mediated mitochondrial transfer, effectively ameliorating oestrogen-deficient osteoporosis. This study provides pharmacological support and novel mechanistic insights for CSA as a promising natural candidate for osteoporosis treatment.

PMID 42475869
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