6182. Midazolam

Nomenclature

CAS number: 59467-70-8
8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine.
C18H13ClFN3; mol wt 325.77.
C 66.36%, H 4.02%, Cl 10.88%, F 5.83%, N 12.90%.

Description and references

Short-acting deriv of diazepam, q.v. Prepn: R. I. Fryer, A. Walser, DE 2540522; eidem, US 4280957 (1976, 1981 both to Hoffmann-La Roche); A. Walser et al., J. Org. Chem. 43, 936 (1978). LC/MS determn in plasma: E. R. Lepper et al., J. Chromatogr. B 806, 305 (2004); as a probe for cytochrome P450 3A4 activity: H. Kanazawa et al., J. Chromatogr. A 1031, 213 (2004). Series of articles on pharmacology, metabolism, pharmacokinetics, clinical experience: ibid. 2177-2288; Br. J. Clin. Pharmacol. 16, Suppl. 1, 1S-199S (1983). Review of pharmacology and therapeutic use: J. W. Dundee et al., Drugs 28, 519-543 (1984); in treatment of status epilepticus: D. F. Hanley, J. F. Kross, Clin. Ther. 20, 1093-1105 (1998). Clinical evaluation for intranasal treatment of febrile seizures in children: E. Lahat et al., Br. Med. J. 321, 83 (2000).

Chemical structure

Properties

Colorless crystals from ether/methylene chloride/hexane, mp 158-160°. uv max (2-propanol): 220 nm (ε 30000).

Derivative

Maleate.

Nomenclature

CAS number: 59467-94-6
Ro-21-3981/001; Dormicum (Roche).
C18H13ClFN3.C4H4O4; mol wt 441.84.
C 59.80%, H 3.88%, Cl 8.02%, F 4.30%, N 9.51%, O 14.48%.

Properties

Crystals from ethanol/ether, mp 114-117° (solvated). LD50 in male mice (mg/kg): 760 orally; 86 i.v. See L. Pieri et al., Arzneim.-Forsch. 31, 2180 (1981).

Derivative

Hydrochloride.

Nomenclature

CAS number: 59467-96-8
Ro-21-3981/003; Hypnovel (Roche); Ipnovel (Roche); Versed (Roche).
C18H13ClFN3.HCl; mol wt 362.23.
C 59.68%, H 3.90%, Cl 19.57%, F 5.24%, N 11.60%.

Properties

Sol in aqueous solns.

Note

This is a controlled substance (depressant): 21 CFR, 1308.14.

Use

Probe to measure cytochrome P450 3A4 activity.

Therapeutic Category

Anesthetic (intravenous); anticonvulsant; sedative, hypnotic.

Therapeutic Category (Veterinary)

Anesthetic (intravenous); anticonvulsant; sedative; hypnotic.

Keywords

Anesthetic (Intravenous); Anticonvulsant; Sedative/Hypnotic; Benzodiazepine Derivatives