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midazolam

✓ Approved

Rafa Laboratories Ltd · GABRA1 · Small Molecule

What is midazolam?

midazolam is a small molecule developed by Rafa Laboratories Ltd. It is approved for therapeutic indications via injectable (others) or intramuscular (im) injection.

Drug Profile

CompanyRafa Laboratories Ltd
Drug ClassSmall Molecule
Molecular TargetGABRA1, GABRA2, GABRA3, GABRA4, GABRA5
RouteInjectable (Others), Intramuscular (IM) Injection
StatusApproved

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 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Nervous system disordersStatus epilepticus✓ 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.

PubMedAnesthesiology research and practice2026-08-30

Intraoperative Hemodynamic Management and Cerebral Protection During Awake Craniotomy: Evidence-Based Approaches.

Maragh Marc Knezevic MK, Garcia Alanna Pagan AP, Oliinyk Yuliia Y, Acharjee Jayottri J et al.

Awake craniotomy is a standard neurosurgical technique that enables real-time assessment of brain functions during tumor resection, with high success rates. Although highly effective, the procedure is associated with hemodynamic disturbances, including blood pressure variability and impaired cerebral perfusion, compromising intraoperative safety. A focused literature search of PubMed, Embase, and Google Scholar was performed to identify relevant studies on intraoperative hemodynamic management during awake craniotomy. Findings were synthesized narratively to summarize current evidence, highlight emerging strategies, and identify knowledge gaps. Hypertension (8%-34%) was the most common disturbance, often triggered by painful surgical stimuli or emergence from sedation, with repeat craniotomy, impaired autoregulation, and glioma pathology as additional risk factors. Hypotension (10%-11%) was linked to perioperative stroke and mortality. Cerebral hypoperfusion contributed to poor outcomes, with stroke up to 23% and neurological morbidity in 68% of patients. Preventive strategies, such as scalp blocks, individualized blood pressure targets, and the use of dexmedetomidine and midazolam, improved intraoperative stability, while short-acting agents, including esmolol and labetalol, were preferred for rapid control. Advanced monitoring modalities, including arterial lines, near-infrared spectroscopy, and cerebral autoregulation indices, enhance safety and support accurate functional mapping. Hemodynamic instability during awake craniotomy influences outcomes. Current evidence supports multimodal prevention, tailored blood pressure control, and short-acting pharmacological agents; practice variation and the lack of randomized trials limit standardization. Looking ahead, advanced monitoring and emerging AI systems may provide new opportunities to enhance cerebral protection and optimize patient safety. This review summarizes evidence on intraoperative hemodynamic control in awake craniotomy, emphasizing strategies that enable maximal safe resection while preserving neurological function.

PubMedCurrent pain and headache reports2026-08-29

Adjunct Medications for Single-Injection Pediatric Regional Blocks: Implications for Peripheral Nerve Blocks.

Jha Sachin Sunny SS

Single-injection peripheral nerve blocks (PNBs) provide excellent perioperative analgesia in children but are limited by finite duration. Pediatric populations were excluded from the major adult adjunct reviews. This narrative review synthesizes the evidence for adjuncts added to local anesthetics for single-injection PNBs and caudal blocks in patients aged 0 to 18 years, including dexamethasone, dexmedetomidine, clonidine, conventional opioids, buprenorphine, magnesium sulfate, midazolam, ketamine, neostigmine, tramadol, nalbuphine, and epinephrine. Across 58 studies, dexmedetomidine (0.5 to 1 mcg/kg) and dexamethasone (0.1 mg/kg perineural) were the best-supported agents, each roughly doubling analgesic duration with acceptable safety. Two network meta-analyses ranked neostigmine highest for caudal duration, but its postoperative nausea and vomiting burden limits use. Clonidine has the longest safety record. Ketamine and midazolam show robust caudal efficacy but unresolved neurotoxicity concerns. Nalbuphine and buprenorphine are promising but under-studied. Tramadol carries pediatric regulatory restrictions, while epinephrine and conventional opioids add little. Dexmedetomidine and dexamethasone are the preferred adjuncts in pediatric regional anesthesia. Adult evidence should not be extrapolated directly given developmental pharmacology and pediatric-specific safety considerations. Prospective trials in true pediatric PNBs and pediatric rebound-pain studies remain the critical evidence gaps.

PubMedClinical pharmacokinetics2026-08-29

Effect of Rivoceranib 200 mg Once Daily on the Pharmacokinetics of a Cocktail Probe Substrate of Cytochrome P450 Enzymes: A Phase I Trial in Healthy Volunteers.

Nguyen David D, Wei Xiaohui Tracey XT, Meng Xianzhang X, Alexander Laura L et al.

Rivoceranib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor with antitumor activity, is metabolized in the liver mostly by cytochrome P450 (CYP)3A4/5. In vitro studies suggest that rivoceranib at clinically relevant concentrations may inhibit metabolism of various CYP substrates. This study evaluated the effects of rivoceranib 200 mg once daily (QD) on the pharmacokinetics of various CYP substrates using the Cooperstown 5+1 cocktail. The dosing regimen of rivoceranib used in this study is similar to the proposed rivoceranib regimen (250 mg QD) in combination with camrelizumab for the treatment of patients with hepatocellular carcinoma. This open-label, fixed-sequence, crossover, drug-drug interaction phase I study evaluated the impact of multiple oral doses of rivoceranib 200 mg QD on the single oral dose pharmacokinetics of CYP enzyme substrates administered in the modified Cooperstown 5+1 cocktail (caffeine 200 mg [CYP1A2], warfarin 10 mg [S-warfarin as CYP2C9 substrate] + vitamin K 10 mg, omeprazole 40 mg [CYP2C19], dextromethorphan 30 mg [CYP2D6], and midazolam 2 mg [CYP3A4]) in 18 healthy volunteers. After fasting, volunteers received a single dose of the Cooperstown 5+1 cocktail on day 1 and rivoceranib plus Cooperstown 5+1 cocktail on day 11. After completing a meal, volunteers received a single dose of rivoceranib on days 6-10 and 12-15. Blood samples for pharmcokinetic analyses of substrates were collected pre-dose and up to 120 h post-Cooperstown 5+1 cocktail dosing on days 1 and 11. Volunteers returned once between days 21 and 25 for safety follow-up. Rivoceranib 200 mg QD decreased the cumulative area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) for caffeine by 20% and maximum observed plasma concentration (Cmax) by 7%, increased S-warfarin AUC0-inf by 1.35-fold and Cmax by 1.05-fold, increased omeprazole AUC0-inf by 2.06-fold and Cmax by 1.64-fold, increased dextromethorphan AUC0-inf by 2.67-fold and Cmax by 1.9-fold, and increased midazolam AUC0-inf by 1.44-fold and Cmax by 1.15-fold. Rivoceranib 200 mg QD may substantially inhibit the metabolism of CYP2D6 substrates. Therefore, concomitant use of CYP2D6 substrate drugs with rivoceranib should be approached with caution, and dose adjustment of substrates of CYP2D6 may be necessary when co-administration cannot be avoided. Rivoceranib 200 mg QD may also exert weak inhibitory effects on the metabolism of CYP3A, CYP2C9, and CYP2C19 substrates. In such cases, close monitoring for substrate-related adverse reactions is recommended, particularly when toxicity is sensitive to increased exposures of these substrate drugs. ClinicalTrials.gov identifier: NCT03561298.

PubMedTurkish journal of anaesthesiology and reanimation2026-08-28

Effect of a Structured Preoperative Educational Video on Maternal Anxiety in Elective Cesarean Section: A Randomized Controlled Trial Using EEG Biomarkers.

Kaushal Ashutosh A, Modak Tamonud T, Jain Anuj A, Jain Shikha S et al.

Preoperative anxiety is common in patients undergoing elective cesarean section and may worsen perioperative outcomes. This study evaluated whether a structured preoperative educational video (SPEV) reduces maternal anxiety, as measured by the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the quantitative electroencephalography (QEEG)-derived theta-beta ratio (TBR). Ninety primigravida women undergoing elective cesarean section with spinal anaesthesia were randomized to a video group (n = 45; SPEV plus routine counseling) or a control group (n = 45; routine counseling only). APAIS was measured at baseline and 30 minutes before surgery. Parietal TBR was recorded at baseline, 30 minutes before surgery, and 1 hour after surgery. Groups were compared using appropriate non-parametric tests, and the correlation between subjective and QEEG-derived measures was assessed. Baseline characteristics were comparable between groups. At 30 minutes before surgery, APAIS scores were lower in the video group than in the control group [11.0 (9.0-12.0) vs. 14.0 (12.0-16.0); P < 0.001). TBR was also lower before surgery (1.20 vs. 1.90; P < 0.001) and at 1 hour postoperatively (1.20 vs. 1.80; P < 0.001). A positive correlation between APAIS scores and TBR was observed 30 minutes before surgery (P=0.48, P < 0.001). Intraoperative midazolam requirement was lower in the video group (11.1% vs. 33.3%, P=0.021). A SPEV significantly reduced preoperative anxiety in women undergoing elective cesarean section, as demonstrated by both subjective and QEEG-derived measures, and was associated with reduced intraoperative anxiolytic requirements.

PubMedChildren (Basel, Switzerland)2026-08-27

Premedication of Pediatric Cardiac Population with Midazolam: Comparison of Oral and Sublingual Administration Regarding Plasma Midazolam Concentration, Clinical Effectiveness, Hemodynamic and Behavioral Outcomes.

Kousi Theofili T, Karafotia Afroditi A, Karageorgos Vlasios V, Gkantinas Georgios G et al.

Background: Midazolam is widely used as a pediatric premedication, but evidence from direct comparisons of oral and sublingual administration in children with congenital heart disease remains limited, particularly that from pharmacokinetic and physiologic data analyzed together. Methods: We conducted a single-center prospective randomized study comparing oral midazolam 0.5 mg/kg with sublingual midazolam 0.3 mg/kg in children undergoing cardiac surgery or catheterization procedures under general anesthesia. Plasma midazolam and 1-hydroxymidazolam concentrations were measured approximately 30 min after administration. Log-transformed concentrations were compared using regression/ANCOVA models adjusted for dose and age. Changes in mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) were analyzed from baseline to 15 and 30 min. Behavioral outcomes included the sedation score, separation from parents, and mask acceptance. Results: Sixty-eight children were randomized; 65 had evaluable pharmacokinetic samples and formed the complete-case pharmacokinetic cohort. Adjusted plasma midazolam concentrations did not differ significantly between the groups, with an adjusted geometric mean ratio for sublingual versus oral administration of 0.98 (95% CI 0.53-1.79; unadjusted p = 0.940; Holm-adjusted p = 1.000). The corresponding ratio for 1-hydroxymidazolam was 1.37 (95% CI 0.55-3.41; unadjusted p = 0.494; Holm-adjusted p = 1.000). HR and SpO2 changes were non-significant between the groups. At 30 min, sublingual administration was associated with a lower adjusted change in MAP compared with oral administration (adjusted difference -12.08 mmHg, 95% CI -19.74 to -4.42; unadjusted p = 0.002, Holm-adjusted p = 0.012). Behavioral outcomes did not differ significantly between the groups. Conclusions: In this prospective randomized pediatric cardiac cohort, oral midazolam 0.5 mg/kg and sublingual midazolam 0.3 mg/kg produced comparable plasma concentrations and similar behavioral outcomes. Sublingual administration was not associated with worse HR or SpO2 responses, although an isolated lower MAP change at 30 min warrants confirmation in larger studies. Sublingual midazolam may represent a feasible lower-dose alternative for premedication in this population.

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