5944. Methadone

Nomenclature

CAS number: 76-99-3
6-Dimethylamino-4,4-diphenyl-3-heptanone; 1,1-diphenyl-1-(2-dimethylaminopropyl)-2-butanone; 4,4-diphenyl-6-dimethylamino-3-heptanone.
C21H27NO; mol wt 309.45.
C 81.51%, H 8.79%, N 4.53%, O 5.17%.

Description and references

Opioid analgesic. Prepn: Eisleb, Office of Publication Board, Department of Commerce Report no. PB-981, 96A; Schultz et al., J. Am. Chem. Soc. 69, 2454 (1947); Easton et al., ibid. 2941 (1947). Resolution: Larsen et al., ibid. 70, 4194 (1948); Howe, Sletzinger, ibid. 71, 2935 (1949); Brode, Hill, J. Org. Chem. 13, 191 (1948); Howe, Tishler, US 2644010 (1953 to Merck & Co.); Zaugg, US 2983757 (1961 to Abbott). Pharmacokinetics in patients with chronic pain: C. E. Inturrisi et al., Clin. Pharmacol. Ther. 41, 392 (1987). Toxicity data: Finnegan et al., J. Pharmacol. Exp. Ther. 92, 269 (1948); Winter, Flataker, ibid. 98, 305 (1950). Review: Eddy, J. Am. Pharm. Assoc. Pract. Pharm. Ed. 8, 536 (1947). Comprehensive description: R. H. Bishara, Anal. Profiles Drug Subs. 3, 365-439 (1974). Review of use in opioid dependence: E. C. Senay, Int. J. Addict. 20, 803-821 (1985). Clinical trial of methadone maintenance vs long-term detoxification: K. L. Sees et al., J. Am. Med. Assoc. 283, 1303 (2000).

Chemical structure

Properties

mp 78°; pptd from solns of pH >6.

Derivative

Hydrochloride.

Nomenclature

CAS number: 1095-90-5
AN-148; Hoechst 10820; Depridol (Gedeon Richter); Dolophine (Lilly); Fenadone; Heptadon (Ebewe); Heptanon (Pliva); Ketalgin (Amino); Mephenon (Federa); Methadose (Mallinckrodt); Physeptone (Glaxo Wellcome).

Properties

Platelets from alcohol + ether, mp 235°. Bitter taste. uv max: 292 nm. Soly (g/100 ml): water 12; alcohol 8; isopropanol 2.4. Practically insol in ether, glycerol. The pH of a 1% aq soln: 4.5-5.6. LD50 orally in rats: 95 mg/kg (Finnegan).

Derivative

l-Form Hydrochloride.

Nomenclature

CAS number: 5967-73-7
Levomethadone hydrochloride; l-Polamidon (HMR).

Properties

Crystals, mp 241°. [α]D20 145° (c = 2.5); [α]D20 169° (c = 2.1 in alc). LD50 s.c. in rats: 44 mg/kg (Winter, Flataker).

Note

This is a controlled substance (opiate): 21 CFR, 1308.12.

Therapeutic Category

Analgesic; in treatment of opioid dependence.

Keywords

Analgesic; Opioids; Diphenylpropylamine Derivatives