4135. Flumazenil

Nomenclature

CAS number: 78755-81-4
8-Fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester; ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate; flumazepil; Ro-15-1788; Anexate (Roche); Lanexat (Roche); Romazicon (Roche).
C15H14FN3O3; mol wt 303.29.
C 59.40%, H 4.65%, F 6.26%, N 13.85%, O 15.83%.

Description and references

Imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. Prepn: W. Haefely et al., EP 27214; M. Gerecke et al., US 4316839 (1981, 1982 both to Hoffmann-La Roche). Specific inhibition of benzodiazepine-receptor binding: W. Hunkeler et al., Nature 290, 514 (1981). Electrophysiological study in animals: P. Pole et al., Arch. Pharmacol. 316, 317 (1981). Antagonist, agonist and inverse agonist properties: S. E. File et al., Psychopharmacology 89, 113 (1986). HPLC determn in human plasma: U. Timm, M. Zell, Arzneim.-Forsch. 33, 358 (1983). Clinical reversal of benzodiazepine-induced sedation: A. Darragh et al., Lancet 2, 8 (1981); eidem, ibid. 1042; B. Ricou et al., Br. J. Anaesth. 58, 1005 (1986). Clinical evaluation in drug overdose: G. F. O'Sullivan et al., Clin. Pharmacol. Ther. 42, 254 (1987). Review of effects in neuropsychiatric disorders: A. L. Malizia, D. J. Nutt, Clin. Neuropharmacol. 18, 215-232 (1995).

Chemical structure

Properties

Crystals from alcohol, mp 201-203°. pKa 1.7. Soly in water: 0.4 g/L. Partition coefficient (n-octanol/aq. sulfate buffer, pH 7.4): 14. LD50 in mice, rats (mg/kg): 4000, 1360 i.p.; 4300, 6000 orally (Hunkeler).

Therapeutic Category

Benzodiazepine antagonist.

Therapeutic Category (Veterinary)

Benzodiazepine antagonist.

Keywords

Benzodiazepine Antagonist