Drug (ID: DG00274) and It's Reported Resistant Information
Name
Midazolam
Synonyms
Dazolam; Dormicum; Midanium; Midazolamum; Midosed; Versed; Midazolam Base; Dormicum (TN); Hypnovel (TN); Midacum (TN); Midazolamum [INN-Latin]; Ro 21-3981; Versed (TN); Midazolam (JAN/INN); Midazolam [INN:BAN:JAN]; 4H-Imidazo[1,5-a][1,4]benzodiazepine, 8-chloro-6-(2-fluoro-phenyl)-1-methyl-, (Z)-2-butenedioate; 8-Chlor-6-(2-fluorphenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepin; 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine; 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5a][1,4]benzodiazepine hydrochloride; 8-Chloro-6-(O-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]-benzodiazepine; 8-Chloro-6-(o-fluorophenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepine
    Click to Show/Hide
Indication
In total 2 Indication(s)
Mood/affect symptom [ICD-11: MB24]
Approved
[1]
Epilepsy/seizure [ICD-11: 8A61-8A6Z]
Phase 3
[1]
Structure
Target Translocator protein (TSPO) TSPO_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C18H13ClFN3
IsoSMILES
CC1=NC=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F
InChI
1S/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3
InChIKey
DDLIGBOFAVUZHB-UHFFFAOYSA-N
PubChem CID
4192
ChEBI ID
CHEBI:6931
TTD Drug ID
D0U6LM
VARIDT ID
DR00684
DrugBank ID
DB00683
Type(s) of Resistant Mechanism of This Drug
  DISM: Drug Inactivation by Structure Modification
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-07: Sleep-wake disorders
Click to Show/Hide the Resistance Disease of This Class
Insomnia [ICD-11: 7A00]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4) [1]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Insomnia [ICD-11: 7A00.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
IPS cells Colon Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
Transcellular transport study assay
Mechanism Description The extraction ratio of metabolism of midazolam (a substrate of CYP3A4) to 1-OH midazolam in hiPSC-IECs was 0.534 +/- 0.009 (%), and decreased to 0.322 +/- 0.009 (%) and 0.0821 +/- 0.0064 (%) in the presence of 0.5 and 10 uM ketoconazole (an inhibitor of CYP3A4), respectively. The extraction ratio in Caco-2 cells was 0.0623 +/- 0.0038 (%) and also decreased to 0.0404 +/- 0.0023 (%) and 0.0414 +/- 0.0032 (%) in the presence of 0.5 and 10 uM ketoconazole, respectively.
References
Ref 1 Application of Intestinal Epithelial Cells Differentiated from Human Induced Pluripotent Stem Cells for Studies of Prodrug Hydrolysis and Drug Absorption in the Small Intestine. Drug Metab Dispos. 2018 Nov;46(11):1497-1506. doi: 10.1124/dmd.118.083246. Epub 2018 Aug 22.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Zhang.