Dihydrocodeine

Title: Dihydrocodeine
CAS Registry Number: 125-28-0
CAS Name: (5a,6a)-4,5-Epoxy-3-methoxy-17-methylmorphinan-6-ol
Additional Names: 6-hydroxy-3-methoxy-N-methyl-4,5-epoxymorphinan; dihydroneopine; drocode
Trademarks: Codhydrine; Dehacodin; DF 118; DH-codeine; Didrate (Penick); Dihydrin; Hydrocodin; Nadeine; Novicodin; Paracodin (Knoll); Parzone (Mallinckrodt); Rapacodin (Knoll)
Molecular Formula: C18H23NO3
Molecular Weight: 301.38
Percent Composition: C 71.73%, H 7.69%, N 4.65%, O 15.93%
Literature References: Prepd by reduction of codeine or neopine: Skita, Franck, Ber. 44, 2862 (1911); Wieland, Koralek, Ann. 433, 269 (1923); Stein, Pharmazie 10, 180 (1955).
Properties: Crystals from methanol + water, mp 112-113°; bp15 248°.
Melting point: mp 112-113°
Boiling point: bp15 248°
Derivative Type: Bitartrate (acid tartrate)
Trademarks: Fortuss (GP); DHC (Napp); Dico
Molecular Formula: C18H23NO3.C4H6O6
Molecular Weight: 451.47
Percent Composition: C 58.53%, H 6.47%, N 3.10%, O 31.89%
Properties: Crystals from methanol, contains 66.8% dihydrocodeine when completely anhydr. mp 192-193° (Stein). The commercial medicinal grade usually melts at 186-190°. [a]D25 -72 to -75° (c = 1 in H2O). One gram dissolves in 4.5 ml water. Sparingly sol in alcohol. Insol in ether.
Melting point: mp 192-193° (Stein)
Optical Rotation: [a]D25 -72 to -75° (c = 1 in H2O)
NOTE: This is a controlled substance (opiate): 21 CFR, 1308.12.
Therap-Cat: Analgesic (narcotic). Antitussive.
Keywords: Analgesic (Narcotic); Antitussive.
Dihydrocodeinone Enol Acetate Dihydroequilin Dihydroisocodeine Dihydromorphine Dihydroresorcinol

Dihydrocodeine
Dihydrocodeine skeletal.svg
Systematic (IUPAC) name
4,5-alpha-epoxy-3-methoxy-17-methylmorphinan-6-ol
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. C (US)
Legal status
S2, S3, S4 depending on dose and other constituents
(AU) Class B (UK) Schedule II (US)
Routes
  • oral
  • subcutaneous
  • intramuscular
  • rectal
  • possibly sublingual / buccal
Pharmacokinetic data
Bioavailability 20%[1]
Metabolism
Mainly hepatic, through CYP3A4 and CYP2D6
Half-life 4 hours[1]
Identifiers
CAS number 125-28-0 N
ATC code N02AA08
PubChem CID 5284543
DrugBank DB01551
ChemSpider 4447600 YesY
UNII N9I9HDB855 YesY
KEGG D07831 YesY
ChEMBL CHEMBL1595 N
Chemical data
Formula C18H23NO3 
Mol. mass 301.38 g/mol
 N (what is this?)  (verify)

Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (as in co-dydramol) or aspirin. It was developed in Germany in 1908 and first marketed in 1911.[2]

Dihydrocodeine is also known as Drocode, Paracodeine and Parzone. Its many brand names include Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Dehace, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Paramol, Remedeine, Dico and DF-118.

Commonly available as tablets, solutions, elixirs, and other oral forms, dihydrocodeine is also available in some countries as an injectable solution for deep subcutaneous and intra-muscular administration. As with codeine, intravenous administration should be avoided, as it could result in anaphylaxis and dangerous pulmonary edema. In past times, dihydrocodeine suppositories were used; however, dihydrocodeine is available in suppository form on prescription.

Dihydrocodeine is used as an alternative or adjunct to codeine for the aforementioned indications. It is available as the following salts, in rough descending order of frequency of use: bitartrate, phosphate, hydrochloride, tartrate, hydroiodide, methyliodide, hydrobromide, and sulfate. The salt to free base conversion factors are 0.67 for the bitartrate, 0.73 for the phosphate, and 0.89 for the hydrochloride.

Dihydrocodeine was developed during the intense international search for more effective antitussives, especially to help reduce the airborne spread of tuberculosis, pertussis, pneumonia, and similar diseases, in the years from c.a. 1895 to 1915, and is similar in chemical structure to codeine. Depending on individual metabolism, dihydrocodeine is 100 to 150 percent as strong as codeine[citation needed]. Although dihydrocodeine does have extremely active metabolites, in the form of dihydromorphine and dihydromorphine-6-glucuronide (one hundred times more potent), these metabolites are produced in such small amount that they do not have clinically important effects.[3]

Dihydrocodeine is also the original member and chemical base of a number of similar semi-synthetic opiates such as acetyldihydrocodeine, dihydrocodeine enol acetate, dihydroisocodeine, nicocodeine, and nicodicodeine.