Dihydrocodeine

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

Dihydrocodeine
Clinical data
Other names6α-Hydrocodol
AHFS/Drugs.comInternational Drug Names
Dependence
liability
High
Addiction
liability
High
Routes of
administration
ATC code
Legal status
Legal status
  • AU: S3 (Pharmacist only)
    (S3) (S4) (S8) depending on dose and other constituents
  • BR: Class A2 (Narcotic drugs)
  • CA: Schedule I
  • DE: Prescription only (Anlage III for higher doses)
  • UK: Class B
  • US: Schedule II (Schedule III in drug combination)
Pharmacokinetic data
Bioavailability20%
Metabolism
Mainly hepatic, through CYP3A4 and CYP2D6
MetabolitesDihydromorphine
Nordihydrocodeine
• Others (e.g., conjugates)
Elimination half-life4 hours
Identifiers
  • 4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.004.303
Chemical and physical data
FormulaC18H23NO3
Molar mass301.386 g·mol−1
3D model (JSmol)
SMILES
  • O[C@@H]1[C@@H]2OC3=C(OC)C=CC4=C3[C@@]2([C@H]5CC1)CCN(C)[C@@H]5C4
  • InChI=1S/C18H23NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-13,17,20H,4-5,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1 Y
  • Key:RBOXVHNMENFORY-DNJOTXNNSA-N Y
 NY (what is this?)  (verify)

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 life-threatening pulmonary edema. In the past, dihydrocodeine suppositories were used. Dihydrocodeine is available in suppository form on prescription. Dihydrocodeine is used as an alternative to codeine.

It was first described in 1911 and approved for medical use in 1948. Dihydrocodeine was developed during the search for more effective cough medication, especially to help reduce the spread of tuberculosis, pertussis, and pneumonia in the years from c.a. 1895 to 1915. It is similar in chemical structure to codeine. Dihydrocodeine is twice as strong as codeine. 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 amounts that they do not have clinically significant effects.

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

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