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diazepam (Stesolid / diazepam, Alpharma)

✓ Approved

Pfizer, Inc. · GABRA1 · 小分子

什么是 diazepam？

diazepam 是一种小分子，由Pfizer, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Rectal。

药物档案

商品名Stesolid, diazepam, Alpharma
公司Pfizer, Inc.
药物类别小分子
分子靶点GABRA1, GABRA2, GABRA3, GABRA5
给药途径Rectal
状态Approved
来源： ClinicalTrials.gov, Pfizer, Inc.

作用机制

分子靶点

diazepam 作用于 4 个分子靶点：

GABRA1gamma-aminobutyric acid type A receptor alpha1 subunit (DEE19, ECA4)
GABRA2gamma-aminobutyric acid type A receptor alpha2 subunit (DEE78, EIEE78)
GABRA3gamma-aminobutyric acid type A receptor alpha3 subunit (EPILX2)
GABRA5gamma-aminobutyric acid type A receptor alpha5 subunit (EIEE79, DEE79)
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

diazepam 针对 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Psychiatric disordersAnxiety✓ Approved
Nervous system disordersEpilepsy✓ Approved

相关研究文献

PubMedPharmaceuticals (Basel, Switzerland)2026-10-27

Interventional Effects and Neurometabolic Regulation of a Panax quinquefolius-Containing Herbal Extract (JYF) in Diazepam Withdrawal Syndrome in Mice.

Jiao Yue Y, Gao Chang C, Li Peng P, Liu Yanjiao Y et al.

Background: Long-term benzodiazepine use can lead to dependence and clinically significant withdrawal following discontinuation, highlighting the need to identify effective interventions for withdrawal-associated abnormalities. Methods: High-resolution mass spectrometry was used to characterize the constituents of a Panax quinquefolius-containing herbal extract (JYF) and evaluate their in vivo exposure in rats. Sixty-five C57BL/6 mice were randomly assigned to control, model, and low-, medium-, and high-dose JYF groups. Diazepam withdrawal was induced after 28 days of subcutaneous diazepam administration (12 mg/kg), and JYF was administered orally during the peri-withdrawal period for 7 days, beginning 4 days before diazepam discontinuation. Behavioral assessments, electroencephalographic/electromyographic (EEG/EMG) recordings, histopathological analysis, and neurochemical measurements were performed. Network proximity analysis, widely targeted metabolomics, targeted neurotransmitter quantification, and integrated pathway analysis were subsequently performed. Results: A total of 61 constituents were identified in JYF, of which 44 were detected in serum and 34 in brain tissue. Network proximity analysis highlighted genistein, columbamine, jatrorrhizine, and berberine as candidate constituents associated with withdrawal, anxiety/depression and sleep-related modules. JYF attenuated diazepam withdrawal-associated weight loss, anxiety-like behavior, sleep fragmentation, abnormal EEG activity, and elevations in corticosterone and orexin A. Metabolomic analyses revealed disturbances in lipid, energy, and amino acid metabolism, with tryptophan and phenylalanine metabolism emerging as prominent pathways associated with JYF intervention. Diazepam withdrawal also disrupted cerebral monoamine homeostasis, as reflected by increased serotonin and norepinephrine and decreased dopamine levels; these alterations generally shifted toward control levels after JYF intervention. Conclusions: JYF alleviates behavioral and sleep-related abnormalities associated with diazepam withdrawal. Its effects may be associated with alterations in brain metabolic homeostasis, including tryptophan- and phenylalanine-related metabolism and monoaminergic neurotransmission. Genistein and berberine were identified as candidate active constituents that warrant further experimental validation.

PMID 42943314
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PubMedBiomolecules2026-10-27

Mechanism-Dependent Effects of the α5 GABAA Receptor Negative Allosteric Modulator Basmisanil on Spatial Memory.

Moraru Miruna Valeria MV, Zugravu Aurelian A, Barbu Aurelia Cristiana AC, Stoleru Smaranda S et al.

Cognitive impairment may arise through multiple pathophysiological mechanisms, including altered GABAergic neurotransmission, cholinergic dysfunction, and neuroinflammation. This study investigated whether basmisanil, a selective negative allosteric modulator of α5-containing GABAA receptors, attenuates spatial memory impairment induced by diazepam, trihexyphenidyl (THP), or lipopolysaccharide (LPS). Adult male Wistar rats were assigned to three experimental models of memory impairment, each comprising four treatment groups (control, inducing agent, basmisanil, and inducing agent plus basmisanil; n = 7/group). Spatial memory was assessed using the two-trial Y-maze paradigm. The primary outcome (Time Index U) was analyzed using two-way factorial general linear models with sensitivity analyses. Significant interactions between the inducing agent and basmisanil were observed in the diazepam and LPS models, indicating attenuation of memory impairment following basmisanil coadministration, whereas no significant interaction was detected in the THP model. The largest estimated recovery effect was observed in the diazepam model, followed by the LPS model and the THP model, although cross-model comparisons were not statistically significant. Basmisanil alone did not enhance baseline memory performance. These findings indicate that the behavioral effects of α5-containing GABAA receptor modulation are mechanism-dependent and support further investigation of selective α5 negative allosteric modulators for benzodiazepine-associated memory impairment.

PMID 42939683
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PubMedLife (Basel, Switzerland)2026-10-27

Generalized Tetanus in a Four-Month-Old Labrador Retriever: Complete Recovery and One-Year Follow-Up in a Rare Canine Case.

Fernoagă Cristina C, Turbatu Raluca Mihaela RM, Neagu Alexandru Gabriel AG, Pavel Ruxandra R et al.

Tetanus is an infrequent, potentially fatal neurological disease in dogs, caused by tetanospasmin, the neurotoxin of Clostridium tetani, which reaches the central nervous system by retrograde axonal transport and blocks the release of the inhibitory neurotransmitters glycine and γ-aminobutyric acid. Dogs are comparatively resistant to the toxin, and canine reports remain scarce. This report describes generalized tetanus in a four-month-old, 13 kg male Labrador Retriever presented with an axillary wound sustained approximately one month earlier and neurological signs progressing over approximately seven days, from gait disturbance to generalized whole-body rigidity. On examination the dog showed trismus, risus sardonicus, cervical hyperextension, opisthotonos, third-eyelid protrusion, a sawhorse stance, hyperthermia and intermittent respiratory distress. The diagnosis was established clinically, following a structured neurological work-up and exclusion of the principal differentials, as confirmatory assays were unavailable. Total serum calcium was within the reference interval; serum creatine kinase was elevated; and venous blood-gas analysis indicated a mild, compensated metabolic acidosis. Management comprised metronidazole and clindamycin, equine tetanus antitoxin, diazepam, meloxicam and intensive nursing care in a low-stimulation environment. The dog improved from the first day of hospitalization and recovered without residual deficits, with no recurrence over one year of follow-up. The favorable outcome, in a young canine patient for which the literature would predict a guarded prognosis, is consistent with the absence of clinically detectable autonomic and cardiorespiratory dysfunction and with meticulous supportive care.

PMID 42942178
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PubMedNeurology and therapy2026-10-26

Evaluating Bioequivalence of a New, Higher-Concentration Diazepam Nasal Spray for Seizure Clusters Compared with the Current Formulation in Healthy Adults.

Madden Stuart S, Lopez-Toledano Miguel A MA, Ngo Leock Y LY, Carrazana Enrique E et al.

Diazepam nasal spray is an immediate-use seizure medication for seizure clusters in patients with epilepsy aged ≥ 2 years. Currently, administration of 5- and 10-mg age- and weight-based doses requires a single device, and two devices are needed for the 15- and 20-mg doses (1 spray/nostril). This phase 1, open-label, randomized, 2-sequence, 2-treatment, 3-period crossover study in healthy adults examined whether a single 20-mg diazepam nasal spray actuation of a new formulation with a higher diazepam concentration (test formulation) was bioequivalent to two 10-mg actuations of the current formulation (reference formulation). Participants were randomly assigned to receive the test formulation twice and the reference formulation once or the reference formulation twice and the test formulation once. Safety was assessed. Eighty-six participants were assigned 1:1 to each treatment sequence (n = 43 each). The mean plasma diazepam concentration-time profiles following the administration of the test and reference formulations were largely overlapping. Bioequivalence criteria were met for area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0-t) and AUC from time 0 extrapolated to infinity (AUC0-∞) but not met for maximum observed plasma concentration (Cmax). Two patients receiving the test formulation had mild coronavirus disease 2019 during the study; there were no treatment-related or serious treatment-emergent adverse events. A single 20-mg actuation of diazepam nasal spray was bioequivalent to two 10-mg actuations with respect to AUC0-t and AUC0-∞ but not Cmax. There were no new safety signals for either formulation. The single-actuation formulation may represent a valid and simpler alternative for treatment of seizure clusters.

PMID 42932143
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PubMedThe Journal of pharmacology and experimental therapeutics2026-10-26

The phosphodiesterase 4B inhibitor A33 blocks locomotor stimulation by low doses of ethanol and diazepam.

Blednov Yuri A YA, Mason Sonia S, Mayfield Jody J, Sriramoji-Virdi Sindhu S et al.

Nonselective phosphodiesterase type 4 (PDE4) inhibitors (subtypes A-D) such as apremilast significantly reduce voluntary ethanol consumption. The PDE4B inhibitor A33 does not alter apremilast-mediated reductions in drinking but does alter recovery from intoxicating doses of ethanol in C57BL/6J mice. Here, we used A33 to test the hypothesis that PDE4B modulates the effects of low doses of ethanol. A33 (1 mg/kg, i.p.) prevented locomotor stimulation induced by 1.25 and 1.5 g/kg ethanol during the daytime, when mouse activity is normally low, and blocked stimulation by 1.25 g/kg ethanol in the open field. In other behavioral tests, A33 prevented the motivation to escape a stressful situation (hole-board test) and exploratory activity by 1.25 g/kg ethanol (spontaneous alternation test). However, A33 did not alter the anxiolytic effect of 1.25 g/kg ethanol in the elevated plus maze or working memory in the spontaneous alternation test. Similarly, A33 prevented locomotor stimulation by low-dose diazepam (1 mg/kg, i.p.) without altering its anxiolytic effect. Neurochemically, A33 blocked ethanol-evoked dopamine release in the nucleus accumbens, consistent with the behavioral finding that it blocks ethanol-induced locomotor stimulation. Together with evidence that A33 accelerates recovery from intoxication without altering acute tolerance or metabolism, these findings suggest that A33 specifically blocks the stimulant-like properties of low-dose ethanol. SIGNIFICANCE STATEMENT: Apremilast nonselectively inhibits phosphodiesterase type 4 (PDE4) subtypes A-D and reduces alcohol drinking in preclinical and human studies. We use subtype-selective inhibitors to identify the subtype(s) driving anti-drinking effects. The PDE4B inhibitor A33 blocked motor stimulation by low-dose alcohol, which may explain its ability to shorten intoxication. A33 also blocked alcohol-induced dopamine release in a central area of the brain's reward system. A33 may prevent stimulatory behaviors associated with alcohol-induced euphoria in humans, which may reduce drinking.

PMID 42933289
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PubMedFrontiers in immunology2026-10-24

Facial pruritus and stiffness as the initial manifestations of glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus: a case report and literature review.

Zhang Qiang Q, Li Jie J, Tang Jianguang J, Fang Jia J

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and severe phenotype within stiff-person spectrum disorders (SPSD), frequently associated with glycine receptor antibodies (GlyR-Ab). Because typical rigidity and stimulus-sensitive spasms may be absent at disease onset, early diagnosis can be challenging. We report a 52-year-old man who presented with facial pruritus, facial stiffness, limited tongue protrusion, dysphagia, and left lower-limb pain. Early manifestations included diplopia, restricted extraocular movements, dysarthria, restricted mouth opening, involuntary jaw closure resembling trismus, and involuntary tongue biting. Nonspecific oropharyngeal and maxillofacial abnormalities on imaging initially raised concern for infectious multiple cranial neuropathy, tetanus, or orofacial infection; however, antimicrobial therapy and symptomatic treatment with diazepam and pregabalin produced no sustained improvement. The subsequent emergence of neck, truncal, and lower-limb stiffness, gait impairment, perioral hypersensitivity, and stimulus-induced facial muscle contractions prompted reconsideration of SPSD. Needle electromyography (EMG) demonstrated continuous synchronous motor unit activity in agonist and antagonist muscles at rest. Serum antibody testing was positive for glycine receptor 1 immunoglobulin G (GlyR1-IgG), with a reported semiquantitative value of 1:100, whereas serum glutamic acid decarboxylase 65 (GAD65) antibody was negative, supporting the diagnosis of GlyR-Ab-positive PERM. The patient showed marked initial improvement following combined immunotherapy and symptomatic treatment. During regular follow-up, the patient's symptoms progressively improved. At the latest follow-up, diplopia, facial sensory abnormalities, restricted mouth opening, and limb rigidity had resolved. Repeat serum testing at a different laboratory showed persistent GlyR1-IgG positivity, with a reported endpoint titer of 1:100; the two numerical results were not directly comparable because different titration protocols were used. The patient was advised to continue oral mycophenolate mofetil 500 mg twice daily as maintenance therapy. This case illustrates the diagnostic challenges of GlyR-Ab-positive PERM when facial pruritus and cranial-bulbar symptoms precede generalized stiffness. Recognition of evolving stimulus-induced muscle contractions, together with characteristic EMG findings and antibody testing, can help distinguish this presentation from infectious cranial neuropathy, tetanus, and local orofacial disease.

PMID 42920638
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