| Identification | More | [Name]
Midazolam | [CAS]
59467-70-8 | [Synonyms]
MIDAZOLAM-D4 MALEATE
5-a)(1,4)benzodiazepine,8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo(
8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine
Midazolam (base and/or unspecified salts)
MidazolamBaseE.P
4H-Imidazo1,5-a1,4benzodiazepine, 8-chloro-6-(2-fluorophenyl)-1-methyl-
MIDAZOLAM,BP,EP
8-Chloro-6-(o-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine
Midazolam
8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-α][1,4]benzodiazepine | [EINECS(EC#)]
261-774-5 | [Molecular Formula]
C22H13ClD4FN3O4 | [MDL Number]
MFCD08272801 | [Molecular Weight]
445.86 | [MOL File]
59467-70-8.mol |
| Chemical Properties | Back Directory | [Appearance]
White Crystaline Solid | [Melting point ]
161-164°C | [Boiling point ]
496.9±55.0 °C(Predicted) | [density ]
1.3136 (estimate) | [Fp ]
9 °C | [storage temp. ]
Controlled Substance, -20°C Freezer | [solubility ]
Practically insoluble in water, freely soluble in acetone and in ethanol (96 per cent), soluble in methanol. | [form ]
Solid:crystalline | [pka]
pKa 1.7±0.1;6.15± 0.1 (Uncertain) | [Water Solubility ]
54mg/L(24 ºC) | [Usage]
In many countries this product is controlled. An import permit may be required. Anesthetic; anticonvulsant; sedative; hypnotic | [BCS Class]
1 | [LogP]
2.73 | [CAS DataBase Reference]
59467-70-8(CAS DataBase Reference) | [NIST Chemistry Reference]
Midazolam(59467-70-8) |
| Hazard Information | Back Directory | [Description]
Midazolam is the most commonly used parenteral sedative in anaesthetic practice. The structure of midazolam is altered by local changes in pH (tautomerism), and the two different forms confer either water or lipid solubility to the drug . At pH<4 the benzodiazepine nucleus opens because of an ionisable amine group in the molecule's structure, and this increases water solubility. At plasma pH the amine group is incorporated back into the unionised ring form of the molecule, which is highly lipid soluble and diffuses rapidly into the brain. A concentrated preparation (5mgml ?1 ) is available for i.m. injection and absorption is rapid compared with diazepam. | [Chemical Properties]
White Crystaline Solid | [Originator]
Dormicum,Roche,Switz.,1982 | [Uses]
Anti-Depressant | [Uses]
In many countries this product is controlled. An import permit may be required. Anesthetic; anticonvulsant; sedative; hypnotic | [Definition]
ChEBI: Midazolam is an imidazobenzodiazepine that is 4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted by a methyl, 2-fluorophenyl and chloro groups at positions 1, 6 and 8, respectively. It has a role as a GABAA receptor agonist, an anticonvulsant, an anxiolytic drug, an apoptosis inducer, an antineoplastic agent, a muscle relaxant, a sedative, a general anaesthetic and a central nervous system depressant. It is an organochlorine compound, an imidazobenzodiazepine and a member of monofluorobenzenes. | [Manufacturing Process]
Acetic anhydride (7 ml) was added to a solution of 6.16 g of crude 2-
aminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine
in 200 ml of methylene chloride. The solution was added to 200 ml of
saturated aqueous sodium bicarbonate and the mixture was stirred for 20
minutes. The organic layer was separated, washed with sodium bicarbonate,
dried over sodium sulfate and evaporated to leave resinous 2-
acetylaminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-lH -l,4-
benzodiazepine. This material was heated with 40 g of polyphosphoric acid at
150°C for 10 minutes. The cooled reaction mixture was dissolved in water,
made alkaline with ammonia and ice and extracted with methylene chloride.
The extracts were dried and evaporated and the residue was
chromatographed over 120 g of silica gel using 20% methanol in methylene
chloride. The clean fractions were combined and evaporated to yield resinous
8-chloro-3a,4-dihydro-6-(2-fluorophenyl)-1- methyl-4H-imidazo[1,5-a][1,4] -
benzodiazepine.
A mixture of this material with 500 ml of toluene and 30 g of manganese
dioxide was heated to reflux for 1? hours. The manganese dioxide was
separated by filtration over Celite. The filtrate was evaporated and the residue
was crystallized from ether to yield 8-chloro-6-(2-fluorophenyl)-1-methyl-4Himidazo[1,5-a][1,4]benzodiazepine, melting point 152°C to 154°C. The
analytical sample was recrystallized from methylene chloride/hexane.
A warm solution of 6.5 g (0.02 mol) of 8-chloro-6-(2-fluorophenyl)-1-methyl-
4H-imidazo[1,5-a] [1,4]-benzodiazepine in 30 ml of ethanol was combined
with a warm solution of 2.6 g (0.022 mol) of maleic acid in 20 ml of ethanol.
The mixture was diluted with 150 ml of ether and heated on the steam bath
for 3 minutes. After cooling, the crystals were collected, washed with ether
and dried in vacuo to yield 8-chloro-6-(2-fluorophenyl)-1-methyl-4Himidazo[1.5-a] [1,4]-benzodiazepine maleate, melting point 148°C to 151°C. | [Brand name]
Versed (Roche). | [Therapeutic Function]
Anesthetic | [General Description]
Midazolam is a benzodiazepine, sold as Dormicum, Hypnovel?, and Versed as a sedative and treatment for insomnia and seizures. This Snap-N-Spike? Reference Solution is suitable for many GC/MS or LC/MS applications from clinical toxicology and urine drug testing to pain prescription monitoring or forensic analysis. | [Pharmacokinetics]
Midazolam undergoes hepatic oxidative metabolism and has an elimination half-life of 2–4h. The major metabolite is 1-hydroxymidazolam, which is biologically active. Midazolam has been used as a sole hypnotic for TI VA and produces superior procedural amnesia compared with propofol, but CSHT increases significantly when used by continuous infusion, and this delays recovery. Clinical studies demonstrate the inferiority of midazolam in terms of time to onset of desired sedation score, slower recovery, less clear-headedness, and significantly longer period of postoperative amnesia compared with propofol. | [Clinical Use]
Benzodiazepine:
Sedation with amnesia in conjunction with local
anaesthesia, premedication, induction
Status epilepticus (unlicensed) | [Drug interactions]
Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by
erythromycin, clarithromycin and telithromycin
(profound sedation); metabolism possibly accelerated
by rifampicin.
Antidepressants: concentration of oral midazolam
possibly reduced by St John’s wort.
Antifungals: concentration increased by itraconazole,
fluconazole, ketoconazole, posaconazole and
voriconazole (prolonged sedative effect).
Antipsychotics: increased sedative effects; increased
risk of hypotension, bradycardia and respiratory
depression when parenteral benzodiazepines are
given with IM olanzapine.
Antivirals: concentration increased by atazanavir,
boceprevir, efavirenz, indinavir, fosamprenavir,
ritonavir, saquinavir and telaprevir increase risk of
prolonged sedation; avoid with oral midazolam.
Ciclosporin: in vitro studies suggested that
ciclosporin could inhibit the metabolism
of midazolam. However, blood ciclosporin
concentrations in patients given ciclosporin to
prevent graft rejection were considered too low to
result in an interaction.
Cobicistat: avoid with oral midazolam.
Cytotoxics: concentration increased by crizotinib and
nilotinib; concentration reduced by enzalutamide.
Sodium oxybate: enhanced effects of sodium oxybate
- avoid. | [Metabolism]
Metabolised in the liver via the cytochrome P450
isoenzyme CYP3A4. The major metabolite, alpha hydroxymidazolam has some activity; its half-life is less
than 1 hour.
Midazolam metabolites are excreted in the urine, mainly
as glucuronide conjugates. |
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