Dihydrocodeine

Dihydrocodeine

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	US: C (Risk not ruled out)
Dependence liability	Moderate-high
Addiction liability	Moderate-high
Routes of administration	oral subcutaneous intramuscular rectal possibly sublingual / buccal
ATC code	N02AA08 (WHO)
Legal status
Legal status	AU: S3 (Pharmacist only) (S3) (S4) depending on dose and other constituents CA: Schedule I DE: Anlage III (Prescription only) UK: Class B US: Schedule II
Pharmacokinetic data
Bioavailability	20%
Metabolism	Mainly hepatic, through CYP3A4 and CYP2D6
Biological half-life	4 hours
Identifiers
IUPAC name 4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol
Synonyms	6α-Hydrocodol
CAS Number	125-28-0 N
PubChem CID	5284543
IUPHAR/BPS	7594
DrugBank	DB01551 Y
ChemSpider	4447600 Y
UNII	N9I9HDB855
KEGG	D07831 Y
ChEMBL	CHEMBL1595 N
ECHA InfoCard	100.004.303
Chemical and physical data
Formula	C18H23NO3
Molar mass	301.38 g/mol
3D model (Jmol)	Interactive image
SMILES O[C@@H]1[C@@H]2OC3=C(OC)C=CC4=C3[C@@]2([C@H]5CC1)CCN(C)[C@@H]5C4
InChI 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?)

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.

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 or adjunct to codeine for the aforementioned indications. It is available as the following salts, in approximate descending order of frequency of use: bitartrate, phosphate, hydrochloride, tartrate, hydroiodide, methyliodide, hydrobromide, sulfate, and thiocyanate. 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. 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, dihydrocodeine enol acetate, dihydroisocodeine, nicocodeine, and nicodicodeine.