Codeine

Title: Codeine
CAS Registry Number: 76-57-3
CAS Name: (5a,6a)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
Additional Names: methylmorphine; morphine monomethyl ether; morphine 3-methyl ether
Trademarks: Codicept (Sanol)
Molecular Formula: C18H21NO3
Molecular Weight: 299.36
Percent Composition: C 72.22%, H 7.07%, N 4.68%, O 16.03%
Literature References: Present in opium from 0.7 to 2.5%, depending on the source, but mostly prepd by methylation of morphine, q.v. Discussion of structure and bibliography: Small, Lutz, "Chemistry of the Opium Alkaloids," in U.S. Public Health Reports Suppl. No. 103 (Washington, 1932). Prepn of (+)-codeine and racemate: Goto, Yamamoto, Proc. Jpn. Acad. 30, 769 (1954), C.A. 50, 1052h (1956); of (-)-form: E. J. Bijsterveld, H. J. Sinnige, Rec. Trav. Chim. 95, 24 (1976); H. C. Beyerman et al., ibid. 97, 127 (1978). Manuf from morphine: W. R. Heumann, Bull. Narc. X, 15 (1958). Facile synthesis from thebaine, q.v.: W. G. Dauben et al., J. Org. Chem. 44, 1567 (1979). Toxicity of the hydrochloride: Eddy, Sumwalt, J. Pharmacol. Exp. Ther. 67, 127 (1939). Comprehensive description of codeine and codeine phosphate, q.v.: F. J. Muhtadi, M. M. A. Hassan, Anal. Profiles Drug Subs. 10, 93-138 (1981).
Derivative Type: Monohydrate
Properties: Orthorhombic sphenoidal rods or tablets (octahedra) from water or dil alcohol, mp 154-156° (after drying at 80°). Sublimes (when anhydr) at 140-145° under 1.5 mm pressure. Melts to oily drops when heated in an amount of water insufficient for complete soln, crystallizes on cooling. d420 1.32. [a]D15 -136° (c = 2 in alcohol), [a]D15 -112° (c = 2 in chloroform). pK (15°) 6.05; pH of satd aq soln 9.8. One gram dissolves in 120 ml water, 60 ml water at 80°, 2 ml alcohol, 1.2 ml hot alcohol, 13 ml benzene, 18 ml ether, 0.5 ml chloroform; freely sol in amyl alcohol, methanol, dil acids. Almost insol in petr ether or in solns of alkali hydroxides.
Melting point: mp 154-156° (after drying at 80°)
pKa: pK (15°) 6.05; pH of satd aq soln 9.8
Optical Rotation: [a]D15 -136° (c = 2 in alcohol); [a]D15 -112° (c = 2 in chloroform)
Density: d420 1.32
Derivative Type: Hydrochloride
CAS Registry Number: 1422-07-7
Molecular Formula: C18H21NO3.HCl
Molecular Weight: 335.83
Percent Composition: C 64.38%, H 6.60%, N 4.17%, O 14.29%, Cl 10.56%
Properties: Dihydrate, small needles, mp ~280° with some decompn. [a]D22 -108°. One gram dissolves in 20 ml water, 1 ml boiling water, 180 ml alcohol. pH about 5. LD50 s.c. in mice: 300 mg/kg (Eddy, Sumwalt).
Melting point: mp ~280° with some decompn
Optical Rotation: [a]D22 -108°
Toxicity data: LD50 s.c. in mice: 300 mg/kg (Eddy, Sumwalt)
Derivative Type: Sulfate
CAS Registry Number: 1420-53-7
Molecular Formula: (C18H21NO3)2.H2SO4
Molecular Weight: 696.81
Percent Composition: C 62.05%, H 6.36%, N 4.02%, O 22.96%, S 4.60%
Properties: Trihydrate, crystals or cryst powder. One gram dissolves in 30 ml water, 6.5 ml water at 80°, 1300 ml alc. Insol in chloroform or ether. pH: 5.0. Store in airtight containers; protect from light.
NOTE: This is a controlled substance (opiate): 21 CFR, 1308.12.
Therap-Cat: Analgesic (narcotic); antitussive.
Therap-Cat-Vet: Analgesic (narcotic); antitussive.
Keywords: Analgesic (Narcotic); Antitussive.
Codeine Methyl Bromide Codeine N-Oxide Codeine Phosphate Coenzyme A Coffee Oil

Codeine
Codein - Codeine.svg
Codeine3Dan.gif
Systematic (IUPAC) name
(5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682065
Pregnancy cat. C (US)
Legal status Controlled (S8) (AU) Schedule I (CA) POM (UK) Schedule II (US)
Dependence liability Moderate
Routes Oral, intra-rectally, SC, IM
Pharmacokinetic data
Bioavailability ~90% Oral
Metabolism Hepatic, via CYP2D6 (cytochrome P450 2D6)[1]
Half-life 2.5–3 h
Identifiers
CAS number 76-57-3 YesY
ATC code R05DA04
combinations: N02AA59, N02AA79
PubChem CID 5284371
IUPHAR ligand 1673
DrugBank DB00318
ChemSpider 4447447 YesY
UNII Q830PW7520 YesY
KEGG C06174 YesY
ChEBI CHEBI:16714 YesY
ChEMBL CHEMBL485 YesY
Chemical data
Formula C18H21NO3 
Mol. mass 299.364 g/mol
 YesY (what is this?)  (verify)

Codeine or 3-methylmorphine (a naturally occurring methylated morphine) is an opiate used for its analgesic, antitussive, antidiarrheal, antihypertensive, anxiolytic, antidepressant, sedative and hypnotic properties. It is also used to suppress premature labor contractions, myocardial infarction, and has many other potential and indicated uses. It is often sold as a salt in the form of either codeine sulfate or codeine phosphate.

Codeine is the second-most predominant alkaloid in opium, at up to three percent. Although codeine can be extracted from natural sources, a semi-synthetic process is the primary source of codeine for pharmaceutical use. It is considered the prototype of the weak to midrange opioids (tramadol, dextropropoxyphene, dihydrocodeine, hydrocodone, oxycodone).