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diazepam (Stesolid / diazepam, Alpharma)

✓ Approved

Pfizer, Inc. · GABRA1 · Small Molecule

What is diazepam?

diazepam is a small molecule developed by Pfizer, Inc.. It is approved for therapeutic indications via rectal.

Drug Profile

Brand NamesStesolid, diazepam, Alpharma
CompanyPfizer, Inc.
Drug ClassSmall Molecule
Molecular TargetGABRA1, GABRA2, GABRA3, GABRA5
RouteRectal
StatusApproved

Mechanism of Action

Molecular Targets

diazepam acts on 4 molecular targets:

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)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

diazepam is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Psychiatric disordersAnxiety✓ Approved
Nervous system disordersEpilepsy✓ 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.

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.

PubMedNature communications2026-08-27

Temporal drift of sleep-wake representations in hypothalamic neuronal ensembles.

Yan Yudong Y, Calcini Niccolò N, Rusterholz Thomas T, Gutierrez Carolina C et al.

Correlative and causal evidence implicates distinct genetically-defined and evolutionary-conserved hypothalamic neurons in regulating wakefulness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep. The prevailing view is that these circuits govern sleep-wake states by recruiting stable, invariant neuronal substrates, yet, this remains unknown. Here, we show that inhibitory, excitatory, hypocretins/orexins-, and melanin concentrating hormone-expressing neurons in hypothalamus did not exhibit stable state-specific activities using longitudinal single cell calcium imaging in freely-moving, sleeping male mice. Instead, their activity patterns shift across sleep-wake states over time, while the distribution of active neurons in each sleep state remains stable. While sleep deprivation minimally affected the selectivity of these activity patterns, we found that the sleep-promoting drug diazepam recruited NREM sleep-active cells that were previously inactive or wake-active. These findings indicate that while individual neurons exhibit dynamic, state-dependent shifts of their activity, the overall organization of sleep-wake neural populations remains stable.

PubMedPharmaceuticals (Basel, Switzerland)2026-08-27

Possible Signals of Ocular Disorders Associated with Gabapentinoids: A Three-Arm Study.

Murray Mya M, Guirguis Amira A, Deslandes Paul P, Corkery John Martin JM et al.

Background: Gabapentinoids (gabapentin and pregabalin) are medications used to treat epilepsy and diabetic neuropathy. Reports of gabapentinoid-associated adverse drug reactions (ADRs) are increasing. This study aimed to explore these potential signals, with a focus on ocular adverse effects. Methods: A mixed-methods design was adopted, utilising quantitative and qualitative approaches encompassing: (I) a social listening approach using Reddit; (II) a pharmacovigilance retrospective disproportionality analysis study using serious reports to the FDA Adverse Event Reporting System (FAERS) (2015-2025); and (III) a literature review (2014-2025). Results: Reddit data revealed several user-reported adverse ocular effects, including blurred vision, diplopia and photosensitivity, across 78 and 40 identified reactions for gabapentin and pregabalin, respectively. Pharmacovigilance findings identified positive signals for eye disorders with both gabapentinoids compared to active control diazepam, amitriptyline and carbamazepine). Incidental findings highlighted potential discrepancies between FAERS data and undesired effects listed within the manufacturer's literature, with pregabalin exhibiting higher reporting odds than gabapentin for cataract (ROR: 4.55; 95% CI: 2.51-8.26) and blindness (ROR: 2.63; 95% CI: 1.85-3.73). The literature review reinforced eye disorder concerns, specifically retinal effects with gabapentinoids, noting the absence of robust, high-quality research. Nevertheless, it identified a plausible biological mechanism involving the CACNA2D1 receptor in retinal cells of animal models, with evidence of an effect following oral administration of pregabalin. Conclusions: This study suggests an increase in eye disorder reports associated with gabapentinoid use. Further clinical and epidemiological studies are warranted to validate these real-world signals.

PubMedJournal of veterinary internal medicine2026-08-27

Seizures and blindness onset zone in 7 horses undergoing radiographic myelography in lateral recumbency under inhalation anesthesia.

Aleman Monica M, Estell Krista K, Spriet Mathieu M, Cenani Alessia A et al.

Seizures and blindness are potential complications associated with myelography. Describe, classify, and determine onset zone of seizures and blindness in horses undergoing radiographic myelography in lateral recumbency. Seven young adult horses. Retrospective study. Horses with seizures or blindness associated with myelography were included. Three horses with general proprioceptive ataxia and 4 neurologically normal horses (Warmblood = 4, Thoroughbred = 3), ages 9 (range, 3-16) years old. Iohexol (300 mg I/mL) from 50 to 60 mL (0.09-0.1 mL/kg) were administered intrathecally. Six horses had focal facial motor seizures contralateral to the side of recumbency with expansion to generalized seizures in one horse. The seizure onset zone was determined to be the right parietal cortex based on electroencephalography. Absent menace response of the left eye with bilateral normal dazzle and pupillary light reflexes were supportive of cortical blindness (right occipital cortex) in 5 horses. Seizures were managed using short- (diazepam, 3 horses; midazolam, 2; both, 1) and long-term (phenobarbital = 2/6) antiseizure medications with clinical resolution within 2-8 h post-myelogram. Blindness resolved within 8-48 h post-myelogram. Contralateral focal facial motor seizures and blindness with an onset zone in the parietal and occipital cerebral cortex, respectively, ipsilateral to the side of recumbency are possible adverse effects with characteristic features in horses undergoing radiographic myelography in lateral recumbency. These signs are transient with full resolution of seizures within hours and up to 2 days for the blindness.

PubMedJournal of child neurology2026-08-26

Safety and Local Tolerability of Diazepam Nasal Spray for Children With Epilepsy Aged 2-5 Years: Final Results of a Phase 1/2a Trial.

Segal Eric B EB, Wheless James W JW, Wolf Steven M SM, Zafar Muhammad M et al.

Diazepam nasal spray is approved to treat seizure clusters in patients aged ≥2 years. A long-term safety study in patients aged 6-65 years found a safety profile similar to diazepam rectal gel. We conducted an open-label, phase 1/2a trial of diazepam nasal spray in children with epilepsy aged 2-5 years with motor seizures or seizures with clear alteration of awareness. After a pharmacokinetic period, caregivers were instructed to use diazepam nasal spray (0.5 mg/kg) as needed for frequent seizures or seizure clusters during 180-day safety and optional extension periods. Treatment-emergent adverse events (TEAEs) were assessed. Of 36 enrolled patients, 27 (86.1%) completed both treatment periods (mean duration 15.45 months). Treatment-related TEAEs occurred in 7 patients in the 180-day period and 1 in the optional extension period. No serious treatment-related TEAEs or TEAEs leading to discontinuation/death occurred. The safety profile aligns with patients aged ≥6 years, supporting use in this population.(ClinicalTrials.gov identifier: NCT05076838).

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