THERAPY DOSSIER · th-f9ec3ce2af39

Midazolam, given with TMB4 and atropine

Drug · Midazolam: GABA-A receptor positive allosteric modulator (benzodiazepine site); part of a nerve-agent antidote regimen with atropine and the oxime TMB4

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This record is classified as “NO TRAUMA TRANSLATION”. Read the indication and notes below for the specific context.

Evidence & regulatory context

Mechanism: Midazolam: GABA-A receptor positive allosteric modulator (benzodiazepine site); part of a nerve-agent antidote regimen with atropine and the oxime TMB4
Target: CHEMBL2093872
Injury models: Chemical/toxin
Reported indication: Not recorded
First approval: 1985
Development stage: Not recorded
ChEMBL record: CHEMBL655 ↗
ChEMBL max phase: 4 / 4 (development scale, not regulatory approval)
Synonyms: Midazolam; atropine (co-listed); TMB4/trimedoxime (co-listed)
Note: Not recorded

Clinical trials 6

1 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT03085563 ↗Injury indicationPHASE4completed

Intranasal Midazolam vs Nitrous Oxide Minimal Sedation for Minor Peds ED Procedures

Conscious Sedation · Simple Lacerations Less Than 4 cm · Lumbar Punctures

Enrolment: 63 · Results not recorded

NCT01874717 ↗PHASE3completed

Conscious Sedation With Midazolam in Dentally Anxious Patients (route)

Dental Anxiety

Enrolment: 131 · Results not recorded

NCT01209832 ↗PHASE1terminated

Effect of Tasisulam on CYP3A-mediated Metabolism of Midazolam (PK study)

Advanced Cancer

Enrolment: 11 · Results not recorded

NCT04983615 ↗NAcompleted

Opioid vs Benzodiazepine-based Sedation for Mechanically Ventilated Patients

Mechanically Ventilated Patients

Enrolment: 50 · Results not recorded

NCT01066247 ↗NAcompleted

HRV-changing Premedication on Hemodynamics After Spinal Anesthesia

Hemodynamics After Spinal Anesthesia

Enrolment: 60 · Results not recorded

NCT02515526 ↗NAcompleted

Acute Ethanol on CYP450, NAT2 and P-glycoprotein Activity (midazolam probe)

AOD Effects and Consequences

Enrolment: 16 · Results not recorded

Preclinical evidence 2

2 studies reported at therapy level; 2 evidence entries itemised.

PMID 25976749 ↗2015Reported benefit

Sarin-induced brain damage in rats is attenuated by delayed administration of midazolam.

RatChemical/toxinSprague-DawleyMaleIntramuscularMidazolam 1 mg/kg at 1 min, or 1 or 5 mg/kg at 1 h; TMB4 7.…TMB4 and atropine 1 min after sarin exposure; midazolam either 1 min or 1 h aft…

Model: Sarin poisoning at 1.2 LD50 (108 micrograms/kg, intramuscular) with seizure-induced brain damage

Midazolam at 1 min prevented biochemical, behavioural and histological sequelae; delayed midazolam at 1 h was dose dependent, with 5 mg/kg counteracting acute signs and behavioural impairment and attenuating part of the inflammatory response but not morphological damage, while 1 mg/kg had only a sl…

Extraction: extract · Supplied extraction confidence: 0.75. Machine-extracted fields require source verification.

PMID 30115757 ↗2018Mixed findings

Midazolam-Resistant Seizures and Brain Injury after Acute Intoxication of Diisopropylfluorophosphate, an Organophosphate Pesticide and Surrogate for Nerve Agents.

RatChemical/toxinSprague-DawleyMaleIntramuscular0.2 to 5 mg/kgGiven 10, 40 minutes or later after DFP exposure

Model: Acute diisopropylfluorophosphate (DFP) intoxication producing behavioural and electroencephalographic seizures and status epilepticus, with hippocampal and amygdalar neurodegeneration and neuroinflammation assessed 3 days after exposure

Midazolam controlled seizures, neurodegeneration and neuroinflammation when given 10 minutes after DFP exposure, but efficacy fell substantially when treatment was delayed to 40 minutes or later, confirming benzodiazepine-refractory status epilepticus after organophosphate intoxication.

Extraction: extract · Supplied extraction confidence: 0.72. Machine-extracted fields require source verification.

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