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midazolam (ITI 111 / USL 261 / ITI111)

✓ Approved

Ikano Therapeutics · GABRA1 · Small Molecule

What is midazolam?

midazolam is a small molecule developed by Ikano Therapeutics. It is approved for therapeutic indications via inhaled or intranasal.

Drug Profile

Brand NamesITI 111, USL 261, ITI111
CompanyIkano Therapeutics
Drug ClassSmall Molecule
Molecular TargetGABRA1, GABRA2, GABRA3, GABRA4, GABRA5
RouteInhaled, Intranasal
StatusApproved
Sources: ClinicalTrials.gov, Ikano Therapeutics

Mechanism of Action

Molecular Targets

midazolam acts on 5 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)
GABRA4gamma-aminobutyric acid type A receptor alpha4 subunit ()
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

midazolam is developed for 7 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Nervous system disordersPartial seizuresPhase III
Nervous system disordersEpilepsyPhase III
Nervous system disordersIdiopathic generalised epilepsyPhase III
Nervous system disordersAmnesiaPhase I
Nervous system disordersAnaesthesiaPhase I

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Related Research Articles

PubMedJournal of chromatography. B, Analytical technologies in the biomedical and life sciences2026-10-20

Simultaneous quantification of remimazolam, midazolam, 1'-hydroxymidazolam, and dexmedetomidine in rat plasma by LC-MS/MS: application to biological samples and partial validation in ECMO-derived plasma.

Kakuba Rina R, Sato Yuhki Y, Fujii Yu Y, Nagatsuka Yuka Y et al.

The objective of this study was to develop and validate a sensitive reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of remimazolam (RMZ), midazolam (MDZ), 1'-hydroxymidazolam (1'-OH-MDZ), and dexmedetomidine (DEX) in rat plasma, in compliance with current FDA bioanalytical guidelines. Protein precipitation with esterase inhibition was optimized for 50 μL of rat plasma. Calibration ranges were established to cover the expected in vivo concentrations in pharmacokinetic studies. Full validation was conducted using normal rat plasma, and assay performance was further confirmed by partial validation using extracorporeal membrane oxygenation (ECMO)-derived plasma. The method achieved lower limits of quantification (LLOQs) of 10 ng/mL for RMZ and MDZ, 5.0 ng/mL for 1'-OH-MDZ, and 1.0 ng/mL for DEX. Calibration curves were linear (r2 ≥ 0.99) using weighted (1/x or 1/x2) regression. Within- and between-run accuracy and precision met acceptance criteria (≤15%, and ≤ 20% at the LLOQ). Extraction recovery was consistent, and matrix effects were adequately controlled. RMZ stability was improved through the combined use of sodium fluoride, EDTA-2 K, cooling, and acidification during sample handling. The applicability of the method was demonstrated by quantifying all analytes in plasma samples obtained from rats following intravenous administration. This assay enables simultaneous quantification of clinically relevant sedatives and an active metabolite in small-volume rat samples and may facilitate future pharmacokinetic investigations in preclinical ECMO models.

PMID 42901138
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PubMedMedical journal of the Islamic Republic of Iran2026-10-19

Recurrent Generalized Tonic-Clonic Seizures During Emergence from Propofol Target-Controlled Infusion in a Patient Undergoing Gastrointestinal Endoscopy: A Case Report.

Thanh Lam Vu V

Seizure-like phenomena (SLPs) associated with propofol have been reported in several publications. The mechanisms underlying these phenomena remain incompletely understood. Some studies suggest that rapid fluctuations in propofol concentration within the brain may contribute to the occurrence of SLPs. Therefore, theoretically, target-controlled infusion (TCI) of propofol, which facilitates the achievement and maintenance of more stable drug concentrations compared to bolus injection or manual infusion, could mitigate the risk of SLP occurrences. However, data regarding SLPs during propofol administration via TCI are limited. This case describes a 45-year-old female patient with no history of epilepsy or neurological disorders who developed generalized tonic-clonic seizures immediately following the discontinuation of propofol TCI using the Schnider pharmacokinetic model for sedation during gastroscopy and colonoscopy. These seizures recurred after the first two intravenous doses of midazolam; however, after the third seizure was treated with intravenous diazepam, the patient experienced no further seizures. In addition to further strengthening the evidence regarding rare neurological events associated with propofol, this case suggests that propofol administration via TCI based on the Schnider model may not completely eliminate the risk of drug-induced seizures; thus, anesthesiologists should remain vigilant. Furthermore, the sequential administration of midazolam and diazepam may represent a suitable option for seizure control.

PMID 42894721
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PubMedDrug design, development and therapy2026-10-17

Construction and Validation of a Predictive Model for Voriconazole Treatment Efficacy in Influenza-Associated Pulmonary Aspergillosis Based on Machine Learning.

Zhang Xin X, Zhu Qianqian Q, Tang Sujuan S, Wu Qingwen Q et al.

To analyze risk factors affecting voriconazole efficacy in influenza-associated pulmonary aspergillosis (IAPA) and build interpretable machine learning (ML) predictive models. This retrospective study enrolled voriconazole-treated IAPA patients into a primary retrospective set (Jan 1, 2020-Jul 31, 2025) and a separate temporal external validation set (Aug 1, 2025-Apr 30, 2026). To avoid data leakage, the primary set was stratified by treatment response and randomly split at a 7:3 ratio into training and internal validation set prior to feature screening. Forty-two baseline candidate variables were collected. Feature selection was performed exclusively within the training dataset via univariate screening, 10-fold cross-validated Least Absolute Shrinkage and Selection Operator (LASSO), and Variance Inflation Factor (VIF) collinearity filtering. Parallel multivariate logistic regression was performed to identify independent predictors without additional stepwise elimination. Validation sets were only used for model performance evaluation. Seven ML algorithms were constructed, and SHapley Additive exPlanations (SHAP) analysis was applied to interpret the best-performing model. Patients in the internal set were categorized into voriconazole-responsive (VR, n=284) and non-responsive (VNR, n=56) groups based on clinical remission, radiological absorption, and reduction of inflammatory biomarkers. Multi-step variable screening retained 11 non-collinear candidate predictors. Multivariate logistic regression identified four independent predictors for poor therapeutic response: ICU admission, concomitant midazolam use, elevated baseline neutrophil percentage, and reduced baseline platelet count. The CatBoost model achieved the optimal discrimination, with internal-validation AUC = 0.88 (95% CI: 0.87-0.88) and temporal external-validation AUC = 0.83 (95% CI: 0.70-0.94). Decision Curve Analysis (DCA) demonstrated that all seven models yielded positive net clinical benefit across the threshold probability range of 0.00-0.90. SHAP analysis further illustrated the important contribution of ICU admission and midazolam to prediction outcomes, with partial discrepancy from multivariate logistic regression feature ranking. This study identified four independent predictors of voriconazole efficacy in IAPA patients. The established CatBoost model delivers stable, interpretable prediction to guide individualized voriconazole therapy for IAPA.

PMID 42890834
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PubMedLaboratory animal research2026-10-15

Faster immobilization and recovery with remimazolam compared to midazolam in medetomidine-butorphanol balanced anesthesia in male Sprague-Dawley rats: a randomized crossover study.

Sasaki Takeru T, Watanabe Masaki M, Nakagawa Ryuya R, Inoue Riyu R et al.

Balanced injectable anesthesia combining an α2-adrenoceptor agonist, a benzodiazepine, and an opioid is widely used in laboratory rodents because it provides sedation, muscle relaxation, and analgesia through complementary pharmacological mechanisms. In Japan, a mixture of medetomidine, midazolam, and butorphanol (MMB) is commonly used as an injectable anesthetic regimen in mice and rats. Remimazolam is an ultra-short-acting benzodiazepine that is rapidly metabolized by tissue esterases and produces no active metabolites. Because of its rapid metabolism and predictable pharmacokinetic profile, remimazolam has attracted attention as a sedative agent in clinical anesthesia and procedural sedation. Replacing midazolam with remimazolam generates a novel balanced anesthetic combination consisting of medetomidine, remimazolam, and butorphanol (MRB). Although this regimen has been investigated in mice, its anesthetic characteristics in rats have not yet been fully evaluated. The present study aimed to compare the anesthetic and physiological effects of MMB and MRB anesthesia in Sprague-Dawley (SD) rats. Both mixtures induced anesthesia in all animals. The MRB regimen produced faster immobilization than the MMB regimen, whereas the time to loss of righting reflex did not differ significantly between regimens. Reflex-based anesthetic depth during the observation period was comparable between the two regimens. Physiological monitoring revealed regimen-dependent differences in time-course dynamics, particularly for oxygen saturation and respiratory rate. For oxygen saturation, pointwise comparisons showed no significant difference after Holm correction, whereas the area under the curve (AUC) analysis did show a significant difference. Linear mixed-effects modeling (LMM) further demonstrated significant group, time, and group × time interaction effects for oxygen saturation, and significant time and group × time interaction effects for respiratory rate. Recovery after atipamezole (ATI) administration was faster in the MRB group, as shown by both return of righting reflex and behavioral recovery score analyses. MRB produced a reflex-score profile comparable to that of MMB while accelerating early immobilization and antagonist-assisted recovery. Substitution of midazolam with remimazolam also altered SpO₂ and respiratory-rate trajectories. MRB may therefore be useful when rapid recovery is desired. However, comparability was limited to the reflex-based scoring system; these findings do not establish equivalence for painful or invasive surgical procedures.

PMID 42875808
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PubMedJournal of anesthesia2026-10-15

Propofol injection discomfort recall after monitored anesthesia care or general anesthesia: a prospective observational cohort study.

Mai Dylan D, Rowshan Kiana K, Modha Dolly D, Chiou Katie K et al.

Pain during propofol injection is common, yet little is known about how often patients remember this experience after anesthesia or which perioperative factors influence memory formation during induction. In this prospective single-center observational cohort study, English-speaking adults (≥ 18 years) receiving propofol under general anesthesia (GA) or monitored anesthesia care (MAC) were enrolled. Perioperative characteristics, intravenous access details, anesthetic medications and clinician-observed injection pain were recorded. On postoperative day 1, patients were interviewed using a standardized questionnaire assessing recall of discomfort during induction. Univariate and multivariate logistic regression analyses calculated adjusted odds ratios (aOR) and identified factors associated with recall. Of the 1,699 enrolled patients, 1,319 completed the postoperative day 1 assessment; 8.1% reported recall of injection discomfort. Multivariate analysis indicated that younger age (aOR = 1.03; 95% CI = 1.01-1.04; p < 0.001), female gender (aOR = 1.69; 95% CI = 1.02-2.82; p = 0.044), hand IV placement (aOR = 2.164; CI 95% = 1.287-3.636; p = 0.004), and absence of midazolam premedication (aOR = 2.62; 95% CI = 1.44-4.78; p = 0.002) were associated with increased recall. Approximately one in twelve patients recalled discomfort during propofol injection. Patient characteristics and modifiable anesthetic practices, particularly premedication and intravenous access site, were associated with memory of propofol injection discomfort. These findings highlight that memory formation during induction represents a distinct and clinically relevant patient-centered outcome.

PMID 42875655
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PubMedJournal of pain and symptom management2026-10-14

Seizure Management in Palliative Care: An Exploratory Cross-sectional Survey of Physician Practices in Germany.

Willert Dr Med Anna-Christin DMA, Ploner Prof Dr Med Christoph J PDMCJ, Gaus Dr Med Verena DMV, Kowski Pd Dr Med Alexander B PDMAB

Seizures pose significant challenges in patients with serious illness, particularly when altered consciousness or dysphagia impair the ability to take antiseizure medication (ASM). However, evidence to inform seizure management in palliative care is limited. Although guidelines exist for epilepsy populations, recommendations for people with serious illness or the end of life are scarce. To characterize seizure management practices and use of ASM in specialized inpatient (SIPC) and outpatient palliative care (SOPC) in Germany. We conducted an exploratory cross-sectional online survey among palliative care physicians in Germany between 08/2023 and 10/2023. The questionnaire covered key domains, including ASM selection, routes of administration, timing and regimens of acute seizure treatment, transition to benzodiazepines (BZD-ASM), ASM discontinuation, and challenges encountered in clinical practice. Among the 111 participating palliative care physicians, 98% reported initiating maintenance ASM, most commonly Levetiracetam (98%) and Midazolam (75%). Most physicians (99%) reported routinely using rescue medication for acute seizures. Midazolam was the most frequently reported first-line rescue medication, preferred in SIPC by 53% and in SOPC by 65%. For second-line treatment of status epilepticus, Levetiracetam was the most frequent choice in SIPC (50%), while Midazolam was preferred in SOPC (52%). Seizure management in palliative care in Germany reflects the specific requirements of patients with serious illness and partly deviates from established epilepsy guidelines. Findings point to a shift towards individualized approaches, including prioritization of BZD-ASM, flexible routes of administration, and increased off-label use. This highlights the need for tailored guidelines and prospective research in palliative care.

PMID 42874890
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