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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

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

PubMedCureus2026-08-30

Recurrent Catatonia in the Setting of Urinary Tract Infection and Medical Comorbidity: A Case Report.

Traugott Paula P, Mimbella Rachel R, Irizarry Flores Jessica C JC, Kyomen Helen H HH

Catatonia is a neuropsychiatric syndrome characterized by disturbances in motor activity, affect, and autonomic function. Although often associated with primary mood or psychotic disorders, it can be precipitated or sustained by systemic infections such as urinary tract infection (UTI). We describe a 60-year-old man with recurrent catatonia and diagnoses of schizophrenia, bipolar disorder, and major neurocognitive disorder, whose latest episode of catatonia, described in this case report, was preceded by psychosocial stress and appeared to be exacerbated by polymicrobial UTI, bacteremia, and urosepsis. He had a history of neuroleptic malignant syndrome (NMS) and an inconsistent response to electroconvulsive therapy (ECT), limiting usual first-line treatment options. During this admission, he developed Klebsiella pneumoniae UTI with Staphylococcus simulans bacteremia and later Pseudomonas aeruginosa urosepsis, in the context of mixed central and nephrogenic diabetes insipidus likely related to long-term lithium therapy. The patient's catatonia proved refractory to very high-dose lorazepam but improved with an intensive, multimodal regimen including intravenous (IV) benzodiazepines (diazepam, midazolam), enteral and subsequently oral lorazepam, zolpidem, memantine, and aggressive treatment of infection and electrolyte abnormalities. He ultimately regained baseline function and was discharged on a slow taper of benzodiazepines and zolpidem. This case illustrates the bidirectional relationship between infection, autonomic and immune dysregulation, and catatonia; highlights practical challenges when treatment with benzodiazepines and ECT is constrained by medical comorbidity; and supports considering adjunctive GABAergic and glutamatergic agents in carefully selected cases of refractory catatonia, under close specialist supervision.

PubMedFitoterapia2026-08-28

Unusual piscidic-acid and isoflavone derivatives from Sophora flavescens Ait. and their hepatoprotective effect.

Wang Yingchao Y, Zhao Yangtao Y, Li Dandan D, Cao Shijie S et al.

Phytochemical investigation of the roots of Sophora flavescens afforded nineteen piscidic acid and isoflavone derivatives, including seven undescribed compounds (1-7) and four compounds (9-12) reported here for the first time as natural products. Comprehensive analysis of 1D and 2D NMR data, aided by GIAO NMR/DP4+ analyses, induced circular dichroism (ICD) spectra, calculated electronic circular dichroism (ECD) spectra, and X-ray diffraction analysis, enabled their structural elucidation. Structurally, compounds 1-4 were characterized as unusual heterodimers of furfural with either a piscidic acid or an isoflavone derivative, linked via a methylene group; compounds 5-7 were unusual heterodimers of an isoflavone glucoside with a piscidic acid derivative. Additionally, the absolute configurations of the known piscidic acid analogs, ethyl 2-(4-hydroxybenzyl)tartrate (16) and monobutyl 2-(4-hydroxybenzyl)tartrate (19), were established for the first time, based on a comparison of their NMR data, optical rotation values, and ECD spectra with those of compound 15. All isolates were tested for in vitro hepatoprotective activity at 10 μM using ethanol induced AML-12 cells, with compounds 1-9, 14, 16, and 17 demonstrating more significant efficacy. The hepatoprotective effect of piscidic acid (14) was further evaluated in the acute alcohol-induced liver injury (AALI) model rats. The results revealed that its administration significantly reduced levels of ALT, AST, and T-CHO while enhancing SOD activity, thus representing the validation of its hepatoprotective activity. Mechanistically, 14 alleviates AALI via the MAPK signaling pathway, as evidenced by the downregulation of p-JNK and p-ERK protein expression.

PubMedPharmaceuticals (Basel, Switzerland)2026-08-27

Differential Dose-Response Behavioural Profiles of Diazepam, Zolpidem and Indiplon in a Two-Trial Y-Maze Paradigm in Rats.

Moraru Miruna Valeria MV, Coman Oana Andreia OA, Zugravu Aurelian A, Stoleru Smaranda S et al.

Background: Benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) act at the benzodiazepine binding site of GABAA receptors but differ in their receptor subtype selectivity and behavioural profiles. Diazepam acts as a non-selective positive allosteric modulator of benzodiazepine-sensitive GABAA receptors, whereas zolpidem and indiplon display preferential affinity for α1-containing receptor subtypes. Although these compounds have been investigated individually in experimental models of exploratory behaviour and cognition, comparative behavioural data obtained using the same experimental protocol remain limited. Methods: This study evaluated the behavioural effects of diazepam, zolpidem and indiplon in male Wistar rats using a two-trial Y-maze paradigm with a 24 h retention interval. Animals received one of three dose levels of each compound before the acquisition trial. Recall-phase behaviour was evaluated using conventional exploration measures together with time- and entry-based preference indices for the previously inaccessible arm. Primary analyses were performed separately for each compound using one-way ANOVA with appropriate post hoc comparisons. Complementary exploratory factorial analyses were subsequently conducted to examine overall behavioural patterns across drug and nominal dose categories. Results: Diazepam produced marked dose-dependent reductions in recall-phase exploration of the previously inaccessible arm and in both exploratory preference indices. In contrast, zolpidem and indiplon reduced exploratory activity during the acquisition phase without significantly affecting recall-phase exploratory behaviour. The complementary factorial analyses identified significant Drug × Nominal Dose Categories interactions across all recall-related endpoints, indicating that behavioural responses across the nominal dose categories differed among the three compound-specific experimental series. The strongest interaction effects were observed for Time Index % (F(6,72) = 10.522, p < 0.001, ηp2 = 0.467) and Entries Index % (F(6,72) = 6.870, p < 0.001, ηp2 = 0.364). Conclusions: Diazepam produced more pronounced dose-dependent alterations in recall-phase exploratory behaviour than zolpidem or indiplon in the experimental conditions employed. The complementary factorial analyses support the interpretation that the three compounds exhibited different behavioural patterns across the nominal dose categories evaluated, while these exploratory comparisons should be interpreted within the constraints of the study design. Overall, the findings contribute to the comparative behavioural characterization of benzodiazepine-site modulators in the two-trial Y-maze paradigm.

PubMedMedicina (Kaunas, Lithuania)2026-08-27

Oxidized Low-Density Lipoprotein Enhances Toll-like Receptor-Mediated Osteoclastogenic Responses in the Absence of Exogenous RANKL: Implications for Inflammatory Osteoclastogenesis in Periodontitis.

Ohgi Kimiko K, Kajiya Hiroshi H, Nagaoka Yoshiyuki Y, Yamamoto Nana N et al.

Background and Objectives: Oxidized LDL (oxLDL) and Toll-like receptor (TLR) signaling are implicated in inflammatory bone loss and periodontitis, but their cooperative effects on osteoclastogenesis remain unclear. We investigated whether TLR2/4 stimulation regulates the transcription of LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1), a receptor for oxLDL, and whether oxLDL enhances TLR-mediated osteoclastogenic responses in the absence of exogenous RANKL. Materials and Methods: Mouse bone marrow cells (BMCs) were differentiated into bone marrow macrophages (BMMs) with M-CSF and stimulated with TLR ligands (Pam3CSK4 for TLR2 and Lipid A for TLR4) and/or oxLDL, with or without exogenous RANKL. Raw264.7 cells were stimulated with TLR ligands or Porphyromonas gingivalis lipopolysaccharide (LPS). LOX-1 transcriptional activity and osteoclastogenic responses were evaluated using luciferase assays, quantitative RT-PCR, and tartrate-resistant acid phosphatase (TRAP) staining. Results: In Raw264.7 cells, stimulation with Pam3CSK4, Lipid A, or LPS significantly increased LOX-1 promoter activity. In BMCs, Pam3CSK4 significantly increased LOX-1 and MyD88 mRNA expression on day 1, whereas expression decreased by day 3; these changes were suppressed by a TLR2 inhibitor. Lipid A significantly increased LOX-1 and MyD88 mRNA expression on day 3, and the increase in LOX-1 expression was inhibited by a TLR4 inhibitor. Functionally, Pam3CSK4 or Lipid A alone increased mononuclear TRAP-positive cells but did not induce multinucleated TRAP-positive cells. In contrast, co-stimulation of oxLDL with either Pam3CSK4 or Lipid A promoted multinucleated TRAP-positive cell formation even in the absence of exogenous RANKL. Conclusions: TLR2/4 stimulation transiently enhanced LOX-1 transcription and expression in association with increased MyD88 expression. TLR ligands cooperated with oxLDL to promote multinucleated TRAP-positive cell formation in the absence of exogenous RANKL, suggesting that inflammatory and metabolic signals may act synergistically during osteoclastogenesis. These findings improve our understanding of how dyslipidemia-associated factors may contribute to inflammatory bone-resorptive diseases, including periodontitis.

PubMedDentistry journal2026-08-26

Evaluation of Systemic Lutein Supplementation on Periodontal Repair in Experimental Periodontitis in Wistar Rats.

Vitória Otávio Augusto Pacheco OAP, Novaes Vivian Cristina Noronha VCN, Furquim Elisa Mara de Abreu EMA, Matheus Henrique Rinaldi HR et al.

Objectives: The aim of this study was to evaluate the influence of systemic lutein (LT) supplementation on the progression of experimental periodontitis (EP) and its impact on mechanical periodontal therapy (SRP) in rats. Methods: A total of 120 male Wistar rats were used, and EP was induced by placing a ligature around the left mandibular first molar. The animals were allocated into four groups: NT (no treatment)/VEH (vehicle), NT/LT, SRP/VEH and SRP/LT. Supplementation was administered daily by oral gavage (0.7 mL/kg of vehicle or 250 mg/kg of LT). Animals were euthanized at 7, 15 and 30 days, and the hemimandibles were collected for histomorphometric analysis of the percentage of bone in the furcation region (PBF), histopathological assessment and immunohistochemical detection of inflammatory mediators (tumor necrosis factor-alpha, interleukin-1β and interleukin-10) and bone markers (tartrate-resistant acid phosphatase and osteocalcin). Results: Systemic LT supplementation, particularly when associated with scaling and root planning (SRP/LT), reduced the intensity and extent of the inflammatory infiltrate, partially decreased immunolabelling for IL-1β and TNF-α, and promoted greater organization of the connective tissue. Higher PBF values and fewer TRAP-positive cells were observed in LT-treated groups. Conclusions: Systemic LT supplementation reduced inflammation and alveolar bone resorption and enhanced the effects of mechanical periodontal therapy.

PubMedCells2026-08-26

Inflammation-Associated Changes in Piezo1 Expression, Mitophagy-Related Markers, and Matrix Dysregulation in an LPS-Stimulated Co-Culture Organoid System.

Raja Kavitha K, Suresh Dineshwary Grace DG, Albeshri Jamila Khalid JK, Rawat Surendra Singh SS et al.

Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degeneration, chronic low-grade inflammation, and disruption of tissue homeostasis. Although the mechanosensitive ion channel Piezo1 has been implicated in OA pathogenesis, its expression may also be modulated by inflammatory stimuli independently of applied mechanical loading. This study established a scaffold-free three-dimensional co-culture organoid model comprising human bone marrow-derived mesenchymal stem cell-derived chondrocyte-like cells and M-CSF/RANKL-differentiated RAW264.7-derived osteoclast-like cells to investigate Piezo1-associated molecular responses, inflammatory signaling, and mitophagy-related markers under lipopolysaccharide (LPS)-induced inflammatory conditions. Osteoclast-like differentiation was validated in parallel monolayer cultures by tartrate-resistant acid phosphatase staining and the presence of multinucleated cells before the corresponding differentiated cultures were used for organoid generation. Histological staining, immunofluorescence, CellTiter-Glo 3D viability assay, lactate dehydrogenase cytotoxicity assay, RT-qPCR, and Western blotting were used to evaluate extracellular matrix formation and inflammatory, catabolic, and mitochondrial quality-control-associated markers. LPS stimulation increased the expression of Piezo1, HIF-1α, phosphorylated CaMKII, NLRP3, cleaved Caspase-1, and MMP13, together with alterations in mitophagy- and autophagy-associated markers. Among the evaluated compounds, curcumin produced the greatest improvement in viability relative to the LPS-treated group and was selected for subsequent molecular analyses. Curcumin treatment was associated with reduced inflammatory and catabolic marker expression and partial preservation of cartilage-associated matrix markers. These findings demonstrate inflammation-associated changes in Piezo1 expression and related molecular markers but do not establish mechanically activated Piezo1 signaling or Piezo1-dependent causality. The organoid system therefore represents an exploratory LPS-induced inflammatory model exhibiting selected OA-relevant molecular and matrix-associated features.

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