2389. Clonazepam

Nomenclature

CAS number: 1622-61-3
5-(2-Chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one; 7-nitro-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one; Ro-5-4023; Iktorivil (Roche); Klonopin (Roche); Rivotril (Roche).
C15H10ClN3O3; mol wt 315.71.
C 57.07%, H 3.19%, Cl 11.23%, N 13.31%, O 15.20%.

Description and references

Benzodiazepine antiepileptic agent with anxiolytic and antimanic properties. Prepn: L. H. Sternbach et al., J. Med. Chem. 6, 261 (1963); O. Keller et al., US 3121076 (1964 to Hoffmann-La Roche). Prepd not claimed: J. Kariss, H. L. Newmark, US 3116203 (1963 to Hoffmann-La Roche). Alternate process: A. Focella, A. I. Rachlin, US 3335181 (1967 to Hoffmann-La Roche). Pharmacology: Guerrero-Figueroa et al., Curr. Ther. Res. 11, 40 (1969); Lechat et al., Therapie 25, 893 (1970); D'Armagnac et al., ibid. 26, 439 (1971). Toxicology: Blum et al., Arzneim.-Forsch. 23, 377 (1973). HPLC determn in plasma: I. F. Bares et al., J. Pharm. Biomed. Anal. 36, 865 (2004). Comprehensive description: W. C. Winslow, Anal. Profiles Drug Subs. 6, 61-81 (1977). Review of pharmacokinetics: D. J. Greenblatt et al, J. Clin. Psychiatry 48, 4-9 (1987); of clinical efficacy in panic attacks: M. H. Pollack, ibid. 12-14; in acute mania: G. Chouinard, ibid. 29-37. Clinical trial in panic disorders: G. Moroz, J. F. Rosenbaum, ibid. 60, 604 (1999).

Chemical structure

Properties

White crystals from ethanol-methylene chloride, mp 236.5-238.5°. uv max (7.5% methanol in isopropanol): 248, 310 nm (ε 14500, 11600). Soly in mg/ml at 25°: acetone 31; chloroform 15; methanol 8.6; ether 0.7; benzene 0.5; water <0.1. pK1 1.5, pK2 10.5. LD50 orally in mice: >4000 mg/kg (Blum).

Note

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

Therapeutic Category

Anticonvulsant.

Therapeutic Category (Veterinary)

Anticonvulsant.

Keywords

Anticonvulsant